Bwk (bilateral wasting kidneys) is a spontaneous recessive mutation caused by a G to A point mutation in the first base of intron 30 of the Col4a4 (collagen, type IV, alpha 4) gene. The mutation maintains the mRNA reading frame, but skips exon 30 resulting in low levels of collagen α 3 α 4 α 5 (IV) trimers that are secreted and incorporated into the glomerular basement membrane. Col4a4 encodes as subunit of type IV collagen, a structural component of basement membranes. Mutations in Col4a4 are associated with type II autosomal recessive Alport Syndrome (hereditary glomerulonephropathy). Mice exhibit the following characteristics: progressive elevated ACR (albumin to creatinine ratio), glomerulosclerosis, inflammatory cell infiltration in the kidneys tubular atrophy, podocyte foot process effacement, and tubular protein casts. Similar to a subset of Alport syndrome patients, mice develop an accumulation of abnormal collagen in the glomerular basement membrane (GBM) as well as GBM lesions. No hearing or eye pathologies are detected.
Of the three genetic backgrounds tested, mice on the DBA/2J (Stock No. 014079) genetic background exhibit higher ACR, earlier onset of protein casts and inflammatory cell infiltration as compared to the original mixed NZO/NON background (Stock No. 005326) and mice on the 129S1/SvImJ background. However,kidneys develop severe end stage renal disease by 12 weeks of age in both the DBA/2J and 129S1 backgrounds. This strain may be useful for studying Alport Syndrome and abnormal collagen IV structure.
