Table 5 of Mansergh, Mol Vis 2004; 10:490-511.

Table 5. Confirmed genes: Nine month Sparctm1cam129Sv/Ev/Mf1Gpi-bb lenses versus Mf1Gpi-bb controls

This table lists significant genes confirmed by PCR defined by accession number and identity. The mean fold change values from the arrays are given as are the mouse chromosomal locations (c/s mouse) where they are known. Where genes of known function have been confirmed by PCR an overview of gene function is provided (comments with OMIM number) and possible roles for these gene in the lens and cataractogenesis are suggested (possible role in Sparc null cataract).

                                       full length
Accession                               accession     c/s     Fold                               Possible role in
 number             Identity             number      mouse   change          Comments           Sparc null cataract
---------   ------------------------   -----------   -----   ------   -----------------------   -------------------
BG075211    Adfp adipose               NM_007408.2     4       6.66   novel 50-kD               Role unknown
            differentiation related                                   membrane-associated
            protein Mm.381                                            protein whose mRNA
                                                                      levels are induced
                                                                      rapidly and maximally
                                                                      after triggering
BG086439    Anxa2 annexin A2 Mm.584    NM_007585.2     9       2.63   ANX2 is an autocrine      Role unknown
                                                                      factor that may enhance   could be involved
                                                                      osteoclast formation      in resorption of
                                                                      and bone resorption       abnormal tissue
                                                                      151740                    by cellular
                                                                                                components of the
                                                                                                immune system
BG074814    C1qa; Complement           NM_007572.1     4       7.42   C1q is composed of 3      Complement can
            component 1, q                                            different species of      mediate clotting,
            subcomponent, alpha                                       chains, called A, B,      chemotaxis,
            polypeptide Mm.370                                        and C (see above for      vascular
                                                                      other 2) C1q binds to     permeability,
                                                                      immunoglobulin            phagocytosis, and
                                                                      complexes with            cell lysis [45]
                                                                      resulting serial          Cell lysis is
                                                                      activation of C1r         noted at later
                                                                      (enzyme), C1s             stages of Sparc
                                                                      (proenzyme) and the       null cataract
                                                                      other 8 components of     [5,6,13,16]
BG087868    C1qb complement            NM_009777.1     4       8.80   C1q, the first            See above, C
            component 1, q                                            subcomponent of C1, has   Complement can
            subcomponent, beta                                        a complicated 18-chain    mediate clotting,
            polypeptide Mm.2570                                       structure: 6 A, 6 B,      chemotaxis,
                                                                      and 6 C chains            vascular
                                                                      120570                    permeability,
                                                                                                phagocytosis, and
                                                                                                cell lysis [45].
                                                                                                Cell lysis is
                                                                                                noted at later
                                                                                                stages of Sparc
                                                                                                null cataract
AW547306    C1qg complement            NM_007574.1     4       5.27   Complement deficiency     See below for
            component 1, q                                            is associated with        complement B
            subcomponent, gamma                                       systematic lupus          chain Complement
            polypeptide (aka                                          erythromatosis            can mediate
            complement component                                      120575                    clotting,
            C1q, C chain) Mm.3453                                                               chemotaxis,
                                                                                                phagocytosis and
                                                                                                cell lysis [45].
                                                                                                Cell lysis is
                                                                                                noted at later
                                                                                                stages of Sparc
                                                                                                null cataract
BG087171    C1r complement             NM_023143.1     6       5.29   C1 is a complex of        Complement can
            component 1, r                                            C1q, C1r, and C1s,        mediate clotting,
            subcomponent Mm.24276                                     activated by complexing   chemotaxis,
                                                                      with antigen or an        vascular
                                                                      acidic macromolecule      permeability,
                                                                      (e.g.DNA) C1r             phagocytosis, and
                                                                      deficiency leads to       cell lysis [45].
                                                                      lupus like                Cell lysis is
                                                                      symptoms/reduced          noted at later
                                                                      resistance to             stages of Sparc
                                                                      infection                 null cataract
                                                                      216950                    [5,6,13,16]
BG087429    C3; Complement component   NM_009778.1    17       3.99   C3 is an acute phase      Complement can
            3 Mm.19131                                                reactant; increased       mediate clotting,
                                                                      synthesis of C3 is        chemotaxis,
                                                                      induced during acute      vascular
                                                                      inflammation              permeability,
                                                                      120700                    phagocytosis, and
                                                                                                cell lysis [45].
                                                                                                Cell lysis is
                                                                                                noted at later
                                                                                                stages of Sparc
                                                                                                null cataract
BG087410    Cd9 CD9 antigen Mm.2956    NM_007657.2     6       2.77   CD9, a member of the      Upregulation may
                                                                      transmembrane-4           play a role in
                                                                      superfamily, interacts    abnormal tissue
                                                                      with integrins and        remodelling
                                                                      other membrane            during
                                                                      proteins, and may         cataractogenesis
                                                                      participate in cell
                                                                      migration and adhesion.
                                                                      CD9 is important in the
                                                                      gamete fusion process
                                                                      at fertilization
BG087382,   Ctsd; Cathepsin D          NM_009983.2     7       9.95   Cathepsin D is one of     May be
BG087383    Mm.231395                                                 the lysosomal             upregulated as a
                                                                      proteinases               result of
                                                                      116840                    increased
                                                                                                requirements of
                                                                                                stressed cells
C79876      EST                        none            3      -5.78   also downregulated in 9   Function unknown
BG087124    Fcgr3 Fc receptor, IgG,    NM_010188.2     1       9.32   CD16 is included in the   Upregulation of
            low affinity III (aka                                     zeta natural killer       components of the
            CD16) Mm.22119                                            cell receptor complex.    immune system
                                                                      Mutations cause           could contribute
                                                                      increased                 to the ocular
                                                                      susceptibility to         inflammation,
                                                                      infection 146740          tissue
                                                                                                destruction, and
                                                                                                that occurs in
                                                                                                Sparc null lenses
                                                                                                at advanced
                                                                                                stages of
BG072156    Fgls-pending fragilis      NM_025378.1     7       7.62   interferon induced        Upregulation of
            Mm.141021                                                 transmembrane protein,    components of the
                                                                      605579                    immune system
                                                                                                could contribute
                                                                                                to the ocular
                                                                                                destruction, and
                                                                                                that occurs in
                                                                                                Sparc null lenses
                                                                                                at advanced
                                                                                                stages of
BG085662    Fn1 fibronectin 1          BC004724.1      1      22.28   Roles in cell             Fn1 is a
            Mm.193099                                                 adhesion, morphology,     component of the
                                                                      and surface               lens capsule[6]
                                                                      architecture. Absence     TGF-beta has
                                                                      may cause loss of         effects on
                                                                      contact inhibition of     expression levels
                                                                      movement in transformed   of Sparc and Fn1,
                                                                      cells Most cells          suggesting some
                                                                      depend on fibronectin     degree of
                                                                      for binding to            co-ordinated
                                                                      collagen 135600           regulation.
                                                                                                fibronectin is a
                                                                                                potent monocyte
BG088898    Gp49a; Glycoprotein 49 A   NM_008147.1    10      22.95   membrane protein, low     Role unknown,
            Mm.196617                                                 homology to human         homology may
                                                                      leukocyte                 suggest immune
                                                                      immunoglobulin-like       system function
AW550167,   Hba-a1 hemoglobin          NM_008218.1    11      -7.00   Major mouse alpha         Downregulation
AW551388,   alpha, adult chain 1                                      hemoglobin (2 identical   may disrupt any
BG073468,   Mm.196110                                                 genes) MGI:85168.         or all normal
BG073469,                                                             Possible roles in         functions in the
BG074904,                                                             normal lenses             lens, leading to
BG086243,                                                             structural (may act as    opacity
BG086422                                                              a crystallin), may have   Downregulation
                                                                      a role in lens iron or    also noted in
                                                                      oxygen metabolism, or     human cataract
                                                                      may be pro-apoptotic      [36]
            Hba-x: Hemoglobin X,       NM_010405.2    11     n/a      Mouse embryonic globin    Expressed in
            alpha-like embryonic                                      homologous to             normal lenses
            chain in Hba complex                                      hemoglobin zeta in man    [26], see Hba-a1
            Mm.141758                                                 142310. not
                                                                      detected on array, but
                                                                      checked as other
                                                                      globins downregulated
            Hbb-b1 hemoglobin beta,    NM_008220.2     7     n/a      not detected on array,    Expressed in
            major chain GeneID:                                       but checked as other      normal lenses
            15129                                                     globins downregulated.    [26], see Hba-a1
                                                                      Homologous to             Cataracts have
                                                                      hemoglobin delta in       been associated
                                                                      man                       with sickle cell
                                                                                                anemia and
            Hbb-b2 hemoglobin, beta    NM_016956.2     7     -10.81   The alpha and beta        Expressed in
            adult minor chain                                         loci determine the        normal lenses
            Mm.233825                                                 structure of the 2        [26], see Hba-a1
                                                                      types of polypeptide
                                                                      chains in adult
                                                                      hemoglobin, Hb A.
                                                                      Hbb-b2 differs by nine
                                                                      amino acids from beta
                                                                      adult major chain
                                                                      (Hbb-b1) [39]
            Hbb-y hemoglobin Y,        NM_008221.2     7     n/a      not detected on array     Expressed in
            beta-like embryonic                                       but checked as other      normal lenses
            chain Mm.35830                                            globins downregulated     [26]  see Hba-a1
BG070071    Hspb1; Heat shock protein  NM_013560.1     5       5.56   Heat-shock proteins       Involved in the
            1 (aka HEAT-SHOCK                                         (HSPs) belong to the      stress response
            PROTEIN 27; HSP27)                                        stress protein family,    probably
            Mm.13849                                                  induced in response to    upregulated as a
                                                                      environmental             result of
                                                                      challenges/               increased cell
                                                                      developmental             stress
                                                                      transitions HSP27
                                                                      protein shows sequence
                                                                      similarity to mammalian
                                                                      (known chaperones)
BG070106    Lcn2 lipocalin 2 Mm.9537   AK002932.1      2       9.60   associated with           Upregulation of
                                                                      neutrophil gelatinase,    this gene may be
                                                                      may function as a         involved in
                                                                      modulator of              cataract induced
                                                                      inflammation, induces     immune reaction,
                                                                      apoptosis in a wide       increased
                                                                      variety of leukocytes,    apoptosis, or
                                                                      participates in the       abnormal iron
                                                                      antibacterial iron        metabolism
                                                                      depletion strategy of
                                                                      the innate immune
                                                                      system. 600181
BG064176    Lgals3: Lectin,            NM_010705.1    14       5.18   may play an important     Upregulation of
            galactose binding,                                        role in both innate and   components of the
            soluble 3 Mm.2970                                         adaptive immunity by      immune system
                                                                      contributing to           could contribute
                                                                      phagocytic clearance of   to the ocular
                                                                      microorganisms and        inflammation,
                                                                      apoptotic cells [46]      tissue
                                                                                                destruction and
                                                                                                that occurs in
                                                                                                Sparc null lenses
                                                                                                at advanced
                                                                                                stages of
BG067456    Lyzs lysozyme Mm.45436     NM_017372.2    10      13.38   catalyzes the             Upregulation of
                                                                      hydrolysis of certain     components of the
                                                                      mucopolysaccharides of    immune system
                                                                      bacterial cell walls.     could contribute
                                                                      Mutations associated      to the ocular
                                                                      with increased            inflammation,
                                                                      resistance to infection   tissue
                                                                      or renal amyloidosis      destruction and
                                                                      153450                    re-organization
                                                                                                that occurs in
                                                                                                Sparc null lenses
                                                                                                at advanced
                                                                                                stages of
BG073671    Mfge8 milk fat             NM_008594.1     7       7.67   Lactadherin is            Role unknown, if
            globule-EGF factor 8                                      expressed by mammary      degraded, may
            protein. (aka                                             epithelial cells as a     contribute to
            lactadherin). Mm.1451                                     cell surface protein,     plaque formation
                                                                      secreted as part of the   in abnormal
                                                                      milk fat globule          lenses
                                                                      membrane  Main
                                                                      constituent of aortic
                                                                      medial amyloid is a
                                                                      50 aa peptide derived
                                                                      from a domain of
BG087418    Ms4a6d                     NM_026835.1    19       5.84   Family of proteins        Increasing
            membrane-spanning                                         related to the            porosity of the
            4-domains, subfamily A,                                   B-cell-specific antigen   lens capsule may
            member 6D Mm.170657                                       CD20  They may            result in
                                                                      represent proteins        alterations in
                                                                      functioning either        osmotic status,
                                                                      directly as               resulting in
                                                                      ligand-gated ion          observed cell
                                                                      channels or as            swelling [6]
                                                                      essential components of   Upregulation of
                                                                      such channels             ion channel
                                                                      MGI:1931900               components may
                                                                                                represent an
                                                                                                attempt to
                                                                                                compensate for
BG085244    Musculus IMAGE: 1064756    AY032898.1      7       3.09   intermediate filament     Upregulation may
            plectin mRNA, 3'UTR                                       binding protein and may   result in further
            Mm.234912                                                 provide mechanical        perturbations in
                                                                      strength to cells and     cell adhesion,
                                                                      tissues by acting as a    migration and
                                                                      cross linking element     morphology
                                                                      of the cytoskeleton
                                                                      Mutations cause
                                                                      muscular dystrophy with
                                                                      epidermolysis bullosa
                                                                      simplex 601282
BG087762    P2rx4 purinergic           NM_011026.1     5       5.25   Activation of P2X         Increasing
            receptor P2X,                                             receptors leads to the    porosity of the
            ligand-gated ion channel                                  opening of nonselective   lens capsule may
            4 Mm.27861                                                cation channels that      result in
                                                                      are permeable to Na+,     alterations in
                                                                      K+, and, in some cases,   osmotic status,
                                                                      Ca(2+) 600846             resulting in
                                                                                                observed cell
                                                                                                swelling [6]
                                                                                                Upregulation of
                                                                                                ion channel
                                                                                                regulators may
                                                                                                represent an
                                                                                                attempt to
                                                                                                compensate for
BG072730    Ppgb protective protein    NM_008906.2     2       3.12   mutations cause           Role unknown
            for beta-galactosidase                                    neuraminidase
            Mm.7046                                                   deficiency with
                                                                      deficiency 256540
BG088310    Psap prosaposin            NM_011179.1    10       3.27   Lysosomal prosaposin      Upregulation may
            Mm.233010                                                 (65 kDa) is a             reflect increased
                                                                      nonenzymic protein that   lysosomal
                                                                      is transported to the     degradation
                                                                      lysosomes in a mannose    requirements by
                                                                      6-phosphate-independent   stressed cells
                                                                      manner [47]
BG084583    Rgs10 regulator of         NM_026418.1     7       4.76   RGS proteins negatively   Upreguation
            G-protein signalling 10                                   regulate signaling        reflects changes
            Mm.18635                                                  pathways involving        in signalling
                                                                      7-transmembrane           patterns brought
                                                                      receptors and             about by
                                                                      heterotrimeric G          increasing
                                                                      proteins 602856           abnormality
BG074704    Rnf128 ring finger         NM_023270.3     X       5.23   type I transmembrane      Upregulation
            protein 128 Mm.27764                                      zinc RING finger          implies higher
                                                                      protein in the            levels of
                                                                      endocytic pathway that    ubiquitinated
                                                                      functions as an E3        proteins targeted
                                                                      ubiquitin ligase          for degradation,
                                                                      Expression of RNF128      implies cells are
                                                                      limits                    stressed
                                                                      activation-induced IL2
                                                                      and IL4 production by T
BG075648    Serping1 serine (or        NM_0097760.1    2       4.68   C1 inhibitor is a         Upregulation of
            cysteine) proteinase                                      plasma protein involved   components of the
            inhibitor, clade G,                                       in the regulation of      immune system
            member 1 Mm.38888                                         the complement cascade    could contribute
                                                                      C1 inhibitor regulates    to the ocular
                                                                      the first component of    inflammation,
                                                                      complement (C1) by        tissue
                                                                      inhibition of the         destruction and
                                                                      proteolytic activity of   re-organization
                                                                      its subcomponents C1r     that occurs in
                                                                      and C1s 606860            Sparc null lenses
                                                                                                at advanced
                                                                                                stages of
BG064802,   Sparc secreted acidic      NM_009242.1    11     -12.60   knocked out in Sp mix     Positive control
BG078305,   cysteine rich                                             mice, positive control
BG072874    glycoprotein Mm.35439                                     for these arrays
BG070062    Spp1: Secreted             NM_009263.1     3      40.65   aka ostepontin. Role      Upregulation of
            phosphoprotein 1                                          in immunosurveillance,    components of the
            Mm.285918                                                 role of colocalization    immune system
                                                                      with CD44 in migration,   could contribute
                                                                      cell fusion, and          to the ocular
                                                                      resorption in             inflammation,
                                                                      osteoclasts plays an      tissue
                                                                      important role in tumor   destruction and
                                                                      growth through the        re-organization
                                                                      enhancement of            that occurs in
                                                                      angiogenesis in vivo      Sparc null lenses
                                                                      LocusID: 20750            at advanced
                                                                                                stages of
BG072750    Tgfbi transforming         NM_009369.1    13      13.05   mutations cause corneal   Sparc and Tgfbi
            growth factor, beta                                       dystrophy 601692          are known to
            induced, also known as                                                              induce each
            beta-IG-H3; BIGH3                                                                   other's
            Mm.14455                                                                            expression under
                                                                                                [29] Array
                                                                                                studies using
                                                                                                glioma cell lines
                                                                                                suggest Tgfbi may
                                                                                                be induced by
                                                                                                Sparc [48]
BG074617    Tgm2 transglutaminase      NM_009373.2     2       3.52   Tgm2 leads to formation   Upregulation
            2, C polypeptide                                          of a cross-linked         implies the
            Mm.18843                                                  protein scaffold in       presence of a
                                                                      cells undergoing          greater than
                                                                      apoptosis. This           usual number of
                                                                      stabilizes cell           dying cells
                                                                      membranes (prevent        Sparc in
                                                                      release of harmful        differentiating
                                                                      intracellular             cartilage is
                                                                      components). TGM2 is      known to be a
                                                                      also the autoantigen in   major target for
                                                                      celiac disease            transglutaminase
                                                                      190196                    crosslinking [49]
BG076072    Ugt1a1; UDP-glucuronosyl   NM_013701.1     1       6.55   induced in transgenic     Upregulation
            transferase 1 family,                                     mice, functions to        implies the need
            member 1 Mm.42472                                         eliminate steroids,       to eliminate
                                                                      heme metabolites and      greater than
                                                                      environmental toxins      normal levels of
                                                                      191740                    toxins or toxic
                                                                                                increased cell

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©2004 Molecular Vision <>
ISSN 1090-0535