Apoe dependent loci for urinary albumin in mice

Apoe and several Apoe receptors have been associated with forms of renal disease but usually their aberrations are considered the consequence of the disease. Objective: We wanted to investigate the effect of Apoe on albuminuria with two independent F2 intercrosses between C57BL/6J and A/J. Methods: In the first cross we used wildtype inbred strains while in the second cross we used B6 Apoe−/− animals with analysis of only the Apoe−/− F2 animals. Urine was collected and albumin and creatinine measured. Results: In the first cross, in the presence of Apoe, we identified three quantitative trait loci (QTL: chromosome (Chr) 2 (LOD 3.5, peak at 70 cM, confidence interval (CI) 28–88 cM); Chr 9 (LOD 2.0, peak 5 cM, CI 5–25 cM); and Chr 19 (LOD 1.9, peak 49 cM, CI 23–54 cM). These were named Uae1, Uae2, and Uae3 respectively. Uae1 was concordant with previously found QTL for renal damage on Chr 3 in the rat and 20p13 in the human. Uae3 was concordant with renal damage QTL on Chr 1 in the rat and 19q13 in the human. Uae2 was concordant only with a rat locus on Chr 8. In the second cross, lacking Apoe, none of these three loci were identified but two new loci were found on Chr 4 (LOD 2.2, peak at 54 cM) and Chr 6 (LOD 2.9, peak at 33 cM) named Uae4 and Uae5, respectively. Uae4 was concordant with a QTL found on rat Chr 5. Conclusion: The dependency on Apoe, the overlap with QTL for cholesterol in similar crosses, the presence of genes encoding Apoe receptors in each of the loci of the first cross, and the concordance with rat and human QTL suggests the Apoe/Apoe‐receptor pathway plays a central role in renal damage.