Table 4 of Mansergh, Mol Vis 2004; 10:490-511.


Table 4. Confirmed genes: Nine month Sparctm1cam129Sv/Ev lenses versus 129Sv/Ev 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).

                                     Unigene
                                   full length
Accession                           accession      c/s       Fold                                      Possible role in
 number           Identity            number      mouse     change              Comments             Sparc null cataract
---------   --------------------   -----------   --------   -------   ----------------------------   --------------------
BG079989    Alb1 albumin 1,        NM_009654.1       5       -14.08   Soluble, monomeric protein     Downregulation of
            Mm.16773                                                  which comprises about          Alb1 may disrupt
                                                                      one-half of the blood serum    cell-cell
                                                                      protein. Functions as a        communication in the
                                                                      carrier protein for            lens. Sparc is known
                                                                      steroids, fatty acids, and     to bind albumin,
                                                                      thyroid hormones, plays a      expression of Alb1
                                                                      role in stabilizing            reduced in Sparc
                                                                      extracellular fluid volume     null mice with
                                                                      103600                         diabetic nephropathy
                                                                                                     [34]
BG077309    Birc5 baculoviral      NM_009689.1      11        -5.46   BIRC5 is an inhibitor of       Lens fiber cells
            IAP                                                       apoptosis (IAP), or            lose their nuclei as
            repeat-containing 5                                       programmed cell death, that    they mature via a
            Mm.8552                                                   is selectively overexpressed   tightly controlled
                                                                      in common human cancers        process of 'arrested
                                                                      603352                         apoptosis' [3,4]
                                                                                                     Downregulation could
                                                                                                     affect migration and
                                                                                                     maturation patterns
                                                                                                     of maturing cells in
                                                                                                     the lens
C75991      Cbx5 chromobox         NM_007626.2      15      -215.70   Heterochromatin protein-1      Downregulation may
            homolog 5                                                 (HP1) is a methyl-lysine       alter gene
            (Drosophila HP1a)                                         binding protein localized at   silencing, thereby
            (aka HP1)                                                 heterochromatin sites, where   changing patterns of
            Mm.28003                                                  it mediates gene silencing     gene expression
                                                                      Involved in the repressive
                                                                      functions of the
                                                                      retinoblastoma protein
                                                                      604478
BG073735    Col1a2 procollagen,    NM_007743.1       6       -36.37   Major constituent of bone,     Collagen fibrils in
            type I, alpha 2                                           extracellular matrix           Sparc null skin are
            Mm.168712                                                 structural constituent         smaller and fewer in
                                                                      conferring tensile strength    number [30] The
                                                                      activity. Mutations and        lens or lens capsule
                                                                      polymorphisms associated       may show a reduction
                                                                      with OI, Ehlers-Danlos         in tensile strength
                                                                      syndrome, Marfan syndrome      as a result of
                                                                      and osteoporosis               collagen
                                                                      120160                         downregulation
BG074327    Col3a1 procollagen,    NM_009930.1       1       -66.77   Fetal (and blood vessel)       Sparc is known to
            type III, alpha 1                                         collagen is also called        interact with
            Mm.234850                                                 collagen III Its synthesis     collagens type I,
                                                                      is defective in                III and IV, also see
                                                                      Ehlers-Danlos syndrome type    Col1a2 above
                                                                      IV 120280
BG085518    Eraf erythroid         NM_133245.1   position    -22.61   ERAF forms a stable complex    EraF may be
            associated factor                    unknown              with free alpha-hemoglobin     important for the
            (aka EDRF or                                              but not beta- or hemoglobin    correct folding and
            AHSP) Mm.218857                                           A (alpha2-beta2). Knockout     stability of Hba-a1
                                                                      mice show shorter              [35] May be
                                                                      erythrocyte halflives.         downregulated with
                                                                      Downregulated in               globins in a
                                                                      transmissible spongiform       co-ordinated fashion
                                                                      encephalopathies (TSEs)        (see below)
                                                                      605821                         downregulation may
                                                                                                     result in incorrect
                                                                                                     Hba-a1 folding
C79876      EST                   none               3       -13.88   also down in 9 month           Function unknown
                                                                      Sparctm1Cam129Sv/Ev/Mf1Gpibb
                                                                      lenses.
BG078478    Gpc3 glypican 3        NM_016697.2       X        -7.79   The glypicans are 1 of the     Loss of this gene
            Mm.22515                                                  2 major families of            is already
                                                                      cell-surface proteoglycans.    implicated in
                                                                      GPC3 is mutated in             cataract
                                                                      Simpson-Golabi-Behmel          downregulation may
                                                                      syndrome, an overgrowth        therefore encourage
                                                                      syndrome that can include      the development of
                                                                      cataract as a feature          opacity
                                                                      312870
BG065213    Grb10 growth factor    NM_010345.1      11       -20.82   Imprinted, but acts            Downregulation of
            receptor bound                                            independently of Igf2. Grb10   growth modulators
            protein 10 Mm.24640                                       as a potent growth             may have effects on
                                                                      inhibitor                      the control of lens
                                                                      601523                         epithelial and fiber
                                                                                                     cell homeostasis and
                                                                                                     maturation
BG076718,   H19 H19 fetal liver    NM_023123.1       7       -29.09   H19 is a developmentally       Downregulation of
BG086671,   mRNA Mm.14802                                             regulated gene with putative   growth modulators
BG087028,                                                             tumor suppressor activity;     may have effects on
BG087529,                                                             loss of H19 expression may     the control of lens
BG087637,                                                             be involved in Wilms           epithelial and fiber
BG087638                                                              tumorigenesis 103280           cell homeostasis and
                                                                      Imprinted, see Igf2, below.    maturation
BG079788,   Hba-a1 hemoglobin      NM_008218.1      11       -52.43   Major mouse alpha              Downregulation may
AW550167,   alpha, adult chain                                        hemoglobin (2 identical        disrupt any or all
AW551388,   1 Mm.196110                                               genes) MGI:85168 Possible      normal functions in
BG072574,                                                             roles in normal lenses:        the lens, leading to
BG072760,                                                             structural (may act as a       opacity
BG073467,                                                             crystallin), may have a role   Downregulation also
BG073468,                                                             in lens iron or oxygen         noted in human
BG073469,                                                             metabolism, or may be          cataract [36]
BG073608,                                                             pro-apoptotic [26]
BG073617,
BG074904,
BG085818,
BG086202,
BG086243,
BG086422
            Hba-x: Hemoglobin      NM_010405.2      11        n/a     Mouse embryonic globin,        not detected on
            X, alpha-like                                             homologous to hemoglobin       array, but checked
            embryonic chain in                                        zeta in man                    as other globins
            Hba complex                                               142310                         downregulated
            Mm.141758                                                                                Expressed in normal
                                                                                                     lenses [26], see
                                                                                                     Hba-a1
            Hbb-b1 hemoglobin      NM_008220.2       7        n/a     not detected on array, but     Expressed in normal
            beta, major chain                                         checked as other globins       lenses [26], see
            GeneID: 15129                                             downregulated. Homologous to   Hba-a1. Cataracts
                                                                      hemoglobin delta in man        have been associated
                                                                                                     with sickle cell
                                                                                                     anemia and
                                                                                                     thalassemia
                                                                                                     [37,38]
AW548291,   Hbb-b2 hemoglobin,     NM_016956.2       7      -146.01   The alpha and beta loci        Expressed in normal
AW548342,   beta adult minor                                          determine the structure of     lenses [26],see
BG072990,   chain Mm.233825                                           the 2 types of polypeptide     Hba-a1
BG085433                                                              chains in adult hemoglobin,
                                                                      Hb A. Hbb-b2 differs by nine
                                                                      amino acids from beta adult
                                                                      major chain (Hbb-b1) [39],
                                                                      141900
            Hbb-y hemoglobin Y,    NM_008221.2       7        n/a     not detected on array, but     Expressed in normal
            beta-like embryonic                                       checked as other globins       lenses [26], see
            chain Mm.35830                                            downregulated.                 Hba-a1
BG064815,   Igf2 insulin-like      NM_010514.1       7       -37.40   IGF-II is a major modulator    Downregulation of
BG073613    growth factor 2                                           of placental and fetal         growth modulators
            Mm.3862                                                   growth. H19 and Igf2 are       may have effects on
                                                                      reciprocally imprinted and     the control of lens
                                                                      form a co-ordinately           epithelial and fiber
                                                                      regulated 130 kb unit in the   cell homeostasis and
                                                                      mouse (controlled by           maturation
                                                                      enhancers, silencers and an
                                                                      imprinting control region
                                                                      (ICR)) [40]
BG066442    Kpna2 karyopherin      NM_010655.2      11        -2.76   maps to same region as         Downregulation may
            (importin) alpha 2                                        Grb10, involved in             result in altered
            Mm.12508                                                  recognition of nuclear         nuclear protein
                                                                      localization signal and        import may affect
                                                                      import of proteins to the      signal transduction
                                                                      nucleus 600685                 may change access of
                                                                                                     newly translated
                                                                                                     trancription factors
                                                                                                     to target DNA. This
                                                                                                     may have knock-on
                                                                                                     effects on
                                                                                                     downstream
                                                                                                     transcription
                                                                                                     patterns
BG085378    Marcks myristoylated   NM_008538.1      10        -2.94   MARCKS is a filamentous        Downregulation of
            alanine rich protein                                      actin crosslinking protein,    Marcks may result in
            kinase C substrate                                        MARCKS may be a regulated      loss of control of
            Mm.30059                                                  crossbridge between actin      cell invasiveness
                                                                      and the plasma membrane,       resulting in the
                                                                      also key regulatory            appearance of
                                                                      molecule. Important in         invadopodia that
                                                                      neural and retinal             extend from the
                                                                      development                    epithelial cells
                                                                      177061                         into the lens
                                                                                                     capsule ECM
BG087241    Mest mesoderm          NM_008590.1       6        -8.81   Imprinted, paternally          Downregulation of
            specific transcript                                       expressed, heterozygosity      growth modulators
            (aka Peg1) Mm.1089                                        causes aberrant maternal       may have effects on
                                                                      behavior, inheritance of       the control of lens
                                                                      defective allele from the      epithelial and fiber
                                                                      father causes growth           cell homeostasis and
                                                                      retardation 601029             maturation
BG063925    Mt2 metallothionein    NM_008630.1       8        -4.25   Metallothioneins: possible     Expressed in lens
            2, LOC330827                                              roles in zinc and copper       epithelium,
            hypothetical gene                                         homeostasis, metal             upregulated in the
            supported by                                              detoxification, regulation     presence of cadmium
            AK046375. Mm.147226                                       or synthesis of                or zinc ions [41]
                                                                      metalloproteins, protection    [42]. Downregulation
                                                                      against reactive oxygen        may affect metal
                                                                      species (ROS)                  metabolism or
                                                                                                     protection against
                                                                                                     ROS Cataract is
                                                                                                     promoted by ROS
                                                                                                     [43]
AW553287    Osf2-pending           NM_015784.1       3       -14.59   may function as a              may also act as an
            osteoblast specific                                       homophilic adhesion molecule   adhesion molecule in
            factor 2 (fasciclin                                       in bone formation              lens, downregulation
            I-like) Mm.10681                                          MGI:1355212                    may affect cell
                                                                                                     adhesivity (see
                                                                                                     Marcks, above) Osf2
                                                                                                     and Sparc are both
                                                                                                     upregulated in a
                                                                                                     mouse model of
                                                                                                     cardiomyopathy
                                                                                                     co-ordinated
                                                                                                     regulation [44]
BG070102    Phtf putative          NM_013629.1       3       -41.45   isolated from subtracted       Downregulation may
            homeodomain                                               cDNA library using mRNAs       have knock-on
            transcription factor                                      isolated from human            effects on
            Mm.25877                                                  erythroleukemic cells          downstream
                                                                      604950                         transcription
                                                                                                     patterns
BG074984,   Sfpq splicing factor   NM_023603.1       4        -5.53   copurified and associated      Downregulation may
BG086821    proline/glutamine                                         with polypyrimidine            affect splicing
            rich (polypyrimidine                                      tract-binding protein, binds   patterns and/or
            tract binding                                             the polypyrimidine tract of    efficiency of
            protein associated)                                       mammalian introns, essential   transcription,
            Mm.140                                                    pre-mRNA splicing factor       therefore may have
                                                                      required early in              knock-on effects on
                                                                      spliceosome formation          downstream
                                                                      605199                         transcription
                                                                                                     patterns
BG064802,   Sparc secreted         NM_009242.1      11       -20.17   gene knocked out in these      Positive control.
BG072874    acidic cysteine rich                                      mice, positive control
            glycoprotein
            Mm.35439
BG086372    Tmpo; Thymopoietin     AK011988.1       10        -5.00   polypeptide thymus hormone,    Downregulation may
            (gene encodes 3                                           pleiotropic actions on         be involved in
            different isoforms)                                       prothymocytes, mature T        effects on immune
            Mm.124                                                    cells, nicotinic               system components
                                                                      acetylcholine receptor, and    seen at a later
                                                                      pituitary corticotrophs May    stage of cataract
                                                                      bind lamin B and               development (see
                                                                      chromosomes, involved in       Figure 4)
                                                                      nuclear architecture and
                                                                      cell cycle control
                                                                      188380

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