Table 4 of
Mansergh, Mol Vis 2004;
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  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  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  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  BG073608, pro-apoptotic  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 , 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 , 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 ,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) , 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 , 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))  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  metalloproteins, protection . Downregulation against reactive oxygen may affect metal species (ROS) metabolism or protection against ROS Cataract is promoted by ROS  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  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