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