title: Tensin2-deficient mice on FVB/N background develop severe glomerular disease.
abstract: Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing α1, α2 and β1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency.
authors: Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki 567-0085, Japan.
authors: Kozue
authors: K
authors: Uchio-Yamada
authors: Yoko
authors: Y
authors: Monobe
authors: Ken-Ichi
authors: K
authors: Akagi
authors: Yoshie
authors: Y
authors: Yamamoto
authors: Atsuo
authors: A
authors: Ogura
authors: Noboru
authors: N
authors: Manabe
mesh_terms: D000818:Animals; D005260:Female; D050533:Glomerular Basement Membrane / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009404:Nephrotic Syndrome / Q000209:etiology* / Q000473:pathology; D050199:Podocytes / Q000473:pathology; D013045:Species Specificity; D000070876:Tensins / Q000172:deficiency*
chemical_list: D000070876:Tensins; C511707:Tns2 protein, mouse