Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim)

Charlotte L. Phillips, Brent Pfeiffer, Alan M. Luger, Craig L. Franklin

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proα2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, α1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, α1(I)2α2(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-α1(I) and anti-α1(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-α1(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.

Original languageEnglish
Pages (from-to)383-391
Number of pages9
JournalKidney International
Volume62
Issue number2
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

Fingerprint

Collagen Type I
Collagen
Basement Membrane
Electron Microscopy
Fibrillar Collagens
Methenamine
Kidney
Osteogenesis Imperfecta
Musculoskeletal System
Periodic Acid
Mesangial Cells
Antibodies
Hematoxylin
Eosine Yellowish-(YS)
Immunohistochemistry
Cell Proliferation
Inflammation
Genes

Keywords

  • Chronic renal disease
  • Extracellular matrix
  • Glomerulosclerosis
  • Mesangium
  • Proα2(I)collagen
  • Renal failure
  • Transgenic mouse model

ASJC Scopus subject areas

  • Nephrology

Cite this

Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim). / Phillips, Charlotte L.; Pfeiffer, Brent; Luger, Alan M.; Franklin, Craig L.

In: Kidney International, Vol. 62, No. 2, 01.01.2002, p. 383-391.

Research output: Contribution to journalArticle

Phillips, Charlotte L. ; Pfeiffer, Brent ; Luger, Alan M. ; Franklin, Craig L. / Novel collagen glomerulopathy in a homotrimeric type I collagen mouse (oim). In: Kidney International. 2002 ; Vol. 62, No. 2. pp. 383-391.
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abstract = "Background: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proα2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, α1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, α1(I)2α2(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-α1(I) and anti-α1(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-α1(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.",
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N2 - Background: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proα2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, α1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, α1(I)2α2(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-α1(I) and anti-α1(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-α1(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.

AB - Background: Oim/oim mice [osteogenesis imperfecta model; homozygous null for the proα2(I) collagen gene] synthesize exclusively the homotrimeric type I collagen isotype, α1(I)3, and are unable to synthesize the normal heterotrimeric type I collagen isotype, α1(I)2α2(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-α1(I) and anti-α1(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-α1(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.

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KW - Extracellular matrix

KW - Glomerulosclerosis

KW - Mesangium

KW - Proα2(I)collagen

KW - Renal failure

KW - Transgenic mouse model

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