Phenotypes for Cfh MGI:2662550 MGI Mouse

premature death ( J:78193 )

• 6 of 26 (23%) of homozygotes die spontaneously by 8 months of age

abnormal kidney capillary morphology ( J:78193 )

• homozygotes that die spontaneously display peripheral capillary loop thickening with deposition of periodic acid-Schiff (PAS)-positive material

increased urine protein level ( J:78193 )

• moribund homozygotes display proteinuria

albuminuria ( J:78193 )

• homozygotes display significantly higher levels of albuminuria than wild-type control mice

• however, serum creatinine levels remain unaffected

hematuria ( J:78193 )

• moribund homozygotes display hematuria

abnormal renal glomerulus basement membrane morphology ( J:78193 )

• homozygotes that die spontaneously display a double-contour appearance of the glomerular basement membrane

abnormal renal glomerulus morphology ( J:78193 )

• homozygotes that die spontaneously display glomerulus hypercellularity, mesangial expansion, and thickening of the capillary walls with double contours

• EM indicates subendothelial electron-dense deposits, formation of new basement membrane on the endothelial side of the deposits, and mesangial cell interposition

increased mesangial cell number ( J:78193 )

• homozygotes that die spontaneously exhibit marked mesangial hypercellularity

mesangial cell interposition ( J:78193 )

• homozygotes that die spontaneously exhibit mesangial cell interposition

glomerulonephritis ( J:78193 )

• by 8 months of age, all homozygotes show histologic evidence of membranoproliferative glomerulonephritis (MPGN); however, renal hemolytic uremic syndrome is not observed and the peripheral blood film is normal

• in response to sheep nephrotoxic serum (NTS) administration, pre-immunized homozygotes show significantly higher mortality than wild-type mice (median survival is 4 vs 14 days, respectively), exhibit severe albuminuria, hemoglobinuria and hypoalbuminemia at 3 days, and develop severe renal disease within 5 days of NTS treatment

expanded mesangial matrix ( J:78193 )

• homozygotes that die spontaneously exhibit marked mesangial matrix expansion

renal glomerular protein deposits ( J:78193 )

• capillary wall and mesangial deposition of both C3 and C9 is observed, whereas IgG shows a predominantly mesangial distribution

renal glomerular immunoglobulin deposits ( J:78193 )

decreased circulating complement protein level ( J:78193 )

• homozygotes exhibit significantly reduced plasma levels of complement protein C3, which are mostly below the detection limit of the assay (30 mg/l)

• in homozygotes, most plasma C3 is in the form of C3b

increased susceptibility to type III hypersensitivity reaction ( J:78193 )

• homozygotes develop membranoproliferative glomerulonephritis (MPGN) due to uncontrolled C3 activation and are hypersensitive to developing renal injury caused by immune complexes

• at 4 days of age, homozygotes show marked capillary wall deposition of C3 and C9 in the glomeruli in the absence of detectable IgG

• at 2 months of age, linear subendothelial electron-dense deposits are noted in the capillary wall in addition to the deposits of C3 and C9 detected by immunofluorescence; however, renal function (as determined by serum albumin, creatinine and urine protein loss) is normal, and there is no localization of IgG in the deposits at this age

• by 8 months of age, all homozygotes display histological evidence of MPGN by light microscopy, whereas none of the heterozygous or wild-type mice show MPGN