Glomerulosclerosis in the Col1a2-deficient mouse model : homotrimer pathogenesis and MMP expression

The Col1a2-deficient (oim) mouse model exclusively synthesizes homotrimeric type I collagen due to the lack of functional pro [alpha] 2(I) collagen chains. The mouse develops a type I collagen glomerulopathy that has previously been shown to initiate postnatally and progress in a gene dose-dependent manner, accumulating type I collagen within the renal mesangium, resulting in podocyte foot effacement and proteinuria. In this study we examine the pre- and post-translational expression of type I collagen and MMPs -2, -3, and -9 in wildtype, heterozygous and Col1a2-deficient glomeruli to determine whether the pathogenic collagen is homotrimeric in nature, and whether alterations in MMP expression play a role in disease progression. Analysis of whole kidney and isolated glomeruli by immunohistochemistry and CNBr peptide mapping suggest that homotrimer is the accumulating type I collagen isotype in sclerotic glomeruli of both affected and heterozygous mice. Steady state MMPs-2, and -3 mRNA levels exhibited significant increases by three months of age, with corresponding protein increases compared to age-matched wildtype mice. Steady state MMP-9 mRNA levels significantly increased by three months of age, but MMP-9 protein expression was significantly decreased. Our findings suggest that upregulation of MMPs-2 and -3 expression is not sufficient to prevent homotrimeric type I collagen deposition and that their induction does not appear to be an initiating event, but may represent a secondary wound response.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biochemistry (MU)

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2009

Author dc:creator

• Roberts-Pilgrim, Anna M., 1977-

Advisor dc:contributor.advisor

• Phillips, Charlotte L.

Statement dc:rights

• OpenAccess.

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/6155

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/6155