Table 5 of
Mansergh, Mol Vis 2004;
10:490-511.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).
Unigene
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
adipocyte
differentiation
103195
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]
complement
120550
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
[5,6,13,16]
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,
vascular
permeability,
phagocytosis and
cell lysis [45].
Cell lysis is
noted at later
stages of Sparc
null cataract
[5,6,13,16]
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
[5,6,13,16]
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
143030
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
degradative
requirements of
stressed cells
C79876 EST none 3 -5.78 also downregulated in 9 Function unknown
month
Sparctm1Cam129Sv/Ev
lenses
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
re-organization
that occurs in
Sparc null lenses
at advanced
stages of
cataract
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
inflammation,
tissue
destruction, and
re-organization
that occurs in
Sparc null lenses
at advanced
stages of
cataract
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.
Degraded
fibronectin is a
potent monocyte
chemoattractant
[45]
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
receptor
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]
[26]
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
thalassemia
[37,38]
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]
141900
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
alpha-crystallins
(known chaperones)
602195
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
re-organization
that occurs in
Sparc null lenses
at advanced
stages of
cataract
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
cataract
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
lactadherin
602281
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
this
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
this
BG072730 Ppgb protective protein NM_008906.2 2 3.12 mutations cause Role unknown
for beta-galactosidase neuraminidase
Mm.7046 deficiency with
beta-galactosidase
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
lymphocytes
300439
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
cataract
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
cataract
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
different
circumstances
[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
metabolites,
suggesting
increased cell
stress
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