Effect of a single nucleotide polymorphism of complement decay accelerating factor (DAF) on proteinuria in BUF/Mna rat

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BUF/Mna strain spontaneously develops proteinuria due to focal and segmental glomeruloscierosis (FSGS). Fine quantitative trait locus (QTL) mapping and synteny analysis clarified that rat homologue of DAF (Daf) located on proteinuria susceptible locus, designated as Purl locus, of rat chromosome 13. A single nucleotide polymorphism in the coding sequence (cSNP) with C-T substitution was found at the nucleotide position 239 of the Daf cDNA in BUF/Mna strain. DNA was obtained in 167 [BUF/Mna x WKYINCrj] F1 x BUF/Mna rats. Urinary protein excretion of these rats were measured. However, analysis of correlation between cSNP and amount of urinary protein excretion has not been completed within the term of the present project. On the other hand, a congenic strain was established in which Purl region of BUF/Mna strain containing Daf was transferred to the genetic background of WKY/NCrj strain. Unilateral nephrectomy was performed in the congenic rats (N=7) and WKY/NCrj rats (N=7) used as controls. At 3 and 9 months, glomerulosclerosis score of the congenic rats was significantly greater than that of WKY/NCrj rats. At 3, 6, and 9 months, urinary protein excretion of the congenic rats was significantly greater than that of WKY/NCrj rats. These results confirmed that Purl region containing Daf had biologic impact on the development of FSGS.