Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim).
BACKGROUND
Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proalpha2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, alpha1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, alpha1(I)2alpha2(I). Previous studies of the oim/oim mouse have focused on the musculoskeletal system, with no systematic evaluation of other organ systems.


METHODS
Multiple tissues from oim/oim, oim/+ (heterozygous) and +/+ (wild-type) mice were examined for gross and histological abnormalities. Tissues were stained with (1) hematoxylin and eosin (to assess lesion formation), (2) picrosirius red (collagen content), and (3) periodic acid methenamine silver (basement membrane). Kidneys were further evaluated ultrastructurally by electron microscopy and immunohistochemically with anti-alpha1(I) and anti-alpha1(III) collagen antibodies.


RESULTS
Histological analyses revealed accumulations of picrosirius red-positive material, consistent with collagen, in glomeruli of 28/29 oim/oim mice, with no evidence of mesangial cell proliferation. Only the most severely affected animals had evidence of increased capillary basement membrane thickening or mild inflammation around the affected glomeruli. Electron microscopy confirmed the presence of fibrillar collagen. Immunohistochemistry with anti-alpha1(I) collagen antibodies confirmed accumulation of type I collagen in the oim/oim glomeruli. The +/+ and oim/+ kidneys had normal mesangium with no evidence of infiltration of collagenous material.


CONCLUSIONS
This study demonstrates the first evidence, to our knowledge, of abnormal glomerular collagen deposition associated with a type I collagen defect. Further in vivo and in vitro studies are necessary to elucidate the mechanistic, functional, and pathological significance of the oim/oim collagen glomerulopathy.
Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri 65212, USA. PhillipsCL@missouri.edu
Charlotte L
CL
Phillips
Brent J
BJ
Pfeiffer
Alan M
AM
Luger
Craig L
CL
Franklin
D000818:Animals; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics*; D024061:Collagen Type III / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D006720:Homozygote; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology*
D024042:Collagen Type I; D024061:Collagen Type III