Background strain and the differential susceptibility of podocyte-specific deletion of Myh9 on murine models of experimental glomerulosclerosis and HIV nephropathy

• Published in: PloS one 2013-07, Vol.8 (7), p.e67839
• Main Authors: Johnstone, Duncan B, Ikizler, Omer, Zhang, Jidong, Holzman, Lawrence B
• Format: Article
• Language: English
• Subjects: Adults; African Americans; Aging; Agriculture; AIDS-Associated Nephropathy - genetics; AIDS-Associated Nephropathy - pathology; Analysis; Animal models; Animals; Anthracyclines; Bioinformatics; Biology; Diabetes; Disease control; Disease Models, Animal; Electrolytes; Female; Gene Deletion; Genetic Predisposition to Disease - genetics; Genotype & phenotype; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - pathology; Hematology; Histopathology; HIV; HIV-1 - physiology; House mouse; Human immunodeficiency virus; Hypersensitivity; Hypertension; Injuries; Kidney diseases; Male; Medicine; Mice; Mice, Congenic; Mice, Inbred C57BL; Mice, Inbred Strains - genetics; Mice, Transgenic; Muscle proteins; Mutation; Myosin; Myosin Heavy Chains; Nephropathy; Nonmuscle Myosin Type IIA - genetics; Organ Specificity - genetics; Podocytes - metabolism; Puromycin; Rodents; Sheep; Urine; Veterinary Science
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0067839

We previously reported that podocyte-specific deletion of Myh9 (conventional myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease but instead results in a predisposition to glomerulosclerosis in response to a second model of glomerular injury. In contrast, other investigators reported that podocyte-specific deletion of Myh9 (PodΔMyh9) resulted in spontaneous glomerulosclerosis in mice on a mixed background, suggesting that the glomerulosclerosis is dependent on background strain. In order to elucidate the cause of this strain dependent effect Podocin::Cre and Myh9(flox) alleles were backcrossed to mouse strain FVB/N, which is highly susceptible to glomerulosclerosis, with the aim of intercrossing susceptible FVB/N and resistant C57BL/6 mice in subsequent congenic analyses. However, after backcrossing mice to FVB/N and aging mice to 28 weeks, we found no evidence of glomerular disease in PodΔMyh9 mice vs control littermates (urine MAC ratio all p>0.05). We also tested C57BL/6 PodΔMyh9 mice for a predisposition to injury from models other than Adriamycin including HIV nephropathy (HIVAN), puromycin nephropathy, and sheep nephrotoxic serum. In the Tg26 model of HIVAN, we found that podocyte-specific deletion of Myh9 resulted in a modest hypersensitivity in adults compared to Tg26+ control littermates (urine MAC ratio, p