A canine autosomal recessive model of collagen type III glomerulopathy

• Published in: Laboratory investigation 2012-10, Vol.92 (10), p.1483-1491
• Main Authors: Rørtveit, Runa, Lingaas, Frode, Bønsdorff, Tina, Eggertsdóttir, Anna V, Grøndahl, Ann M, Thomassen, Ragnar, Fogo, Agnes B, Jansen, Johan H
• Format: Article
• Language: English
• Subjects: 631/208/2489/144; 631/45/612/1250; 692/699/1585/2759; animal model; Animals; Biological and medical sciences; Biotechnology; canine; Collagen Diseases - genetics; Collagen Diseases - metabolism; Collagen Diseases - pathology; collagen type III; Collagen Type III - genetics; Collagen Type III - metabolism; collagenofibrotic; Disease Models, Animal; Dog Diseases - genetics; Dog Diseases - metabolism; Dog Diseases - pathology; Dogs; Female; Fundamental and applied biological sciences. Psychology; Genes, Recessive; Glomerular Mesangium - metabolism; Glomerular Mesangium - ultrastructure; glomerulopathy; hereditary; Humans; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Kidney - immunology; Kidney - pathology; Kidney Diseases - genetics; Kidney Diseases - metabolism; Kidney Diseases - pathology; Laboratory Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; Microscopy, Electron; Microscopy, Electron, Transmission; Microscopy, Fluorescence; nephropathy; Pathology; Pedigree; Rare Diseases - genetics; Rare Diseases - metabolism; Rare Diseases - pathology; research-article
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2012.112

Collagen type III glomerulopathy (Col3GP) is a rare renal disease characterized by massive glomerular accumulations of collagen type III. The disease occurs in both humans and animals, and has been presumed to be heritable with an autosomal recessive inheritance pattern. The pathogenesis is unknown. We describe herein a condition of canine autosomal recessive Col3GP. This spontaneously occurring canine disease was incidentally diagnosed in six mongrel dogs. We then established and studied a pedigree segregating the disease to confirm the genetic nature and inheritance of canine Col3GP. Twenty-nine percent of offspring (14/48) were affected, strongly supporting a simple autosomal recessive inheritance pattern. Kidney specimens were studied by light microscopy, electron microscopy (EM), immunohistochemistry and in situ hybridization. Characteristic findings of Col3GP previously reported in both humans and animals were demonstrated, including massive glomerular collagen type III deposition, and evidence of local mesangial collagen type III synthesis was found. We propose that canine Col3GP may serve as an animal model of human Col3GP. Our initial studies, using simple segregation analysis, showed that the Col3A1 gene was not involved in the disease. This is the first animal model of Col3GP, and further studies of this phenotype in dogs may have the potential to provide information on the pathogenesis and genetics of the disease in both animals and humans, and may thus contribute to the development of treatment regimes.