Gene expression changes during cataract progression in Sparc nullmice: Differential regulation of mouse globins in the lens

[摘要] Purpose: Sparc/osteonectin is a hydroxyapatite, calcium and,collagen binding protein, implicated in tissue morphogenesis, cellproliferation, and repair. Sparc null mice develop sub-corticalposterior cataract with eventual rupture of the lens. We wished tocorrelate genotype with phenotype in these mice via analysis of geneexpression pattern changes leading to disease.Methods: We carried out microarray analysis of adult lenses fromSparctm1cam knockout mice on two strain backgrounds of varyingphenotypic severity at two time points, 4 and 9 months. Labelled cDNAfrom Sparctm1cam knockout and age, strain, and sex matched controllenses was hybridized with HGMP NIA 15,000 clone set arrays.Differential expression was confirmed using semi-quantitative RT-PCR.Results: We have confirmed differential expression of 54 genes. Mostnotably, 5 of the mouse globin genes, Hbb-b1, Hbb-b2, Hba, Hba-x, andHbb-y and an EST, C79876, were significantly downregulatedin 9-month old Sparc null mice from two genetic backgrounds at differentstages of disease. Another downregulated gene, EraF, is involved infolding of globin proteins. Immune response components, includingvarious members of the complement cascade, were upregulated in lenseswith advanced cataract.Conclusions: Five mouse globins show persistent downregulation as aresult of Sparc loss. We speculate as to possible roles of thisphenomenon on pathogenesis of cataract in these mice. Other confirmedgenes allow extension of previous models of cataract development inSparc null mice.

[学科分类] 生物化学/生物物理