Selective breeding for high serum IgA levels from noninbred ddY mice: Isolation of a strain with an early onset of glomerular IgA deposition

An outbred mouse strain known as ddY has been reported to spontaneously develop, late in life, mesangioproliferative glomerulonephritis with a severe glomerular immunoglobulin A (IgA) deposition that mimics human IgA nephropathy. However, the incidence of the disease in this strain is not very high, probably due to its heterogeneous genetic background. Therefore, we attempted to isolate a strain with a high incidence and an early onset of the disease through selection for high serum IgA from the outbred ddY mice. The selection procedure was successful in increasing the serum IgA lever of the selected line and proved effective both in increasing the incidence and in accelerating the onset of the disease. We propose to designate this line of mice 'HIGA', denoting a line with high serum IgA levels. More than half of the mice from the HIGA strain showed a moderate to severe glomerular IgA deposition as early as 25 weeks of age. The severe deposition observed was comparable to that occasionally seen in the original nonselected ddY strain after 40 weeks of age. Thus, we have succeeded in generating a mouse model of IgA nephropathy with a high incidence and an early onset of glomerular IgA deposition. Using light microscopy, progressive and marked mesangial matrix accumulation was shown to develop in HIGA mice. However, they showed only mild proteinuria (100-300 mg/dl) and did not show hematuria.