Genetics, Vol. 179, 693-699, May 2008, Copyright © 2008
doi:10.1534/genetics.107.085142

Quantitative Trait Loci for Urinary Albumin in Crosses Between C57BL/6J and A/J Inbred Mice in the Presence and Absence of Apoe

Carolien Doorenbos*, Shirng-Wern Tsaih{dagger}, Susan Sheehan{dagger}, Naoki Ishimori{dagger}, Gerjan Navis*, Gary Churchill{dagger}, Keith DiPetrillo{dagger},{ddagger} and Ron Korstanje{dagger},§,1

* Department of Internal Medicine and § Department of Pathology and Laboratory Medicine, Division of Medical Biology, University Medical Centre, University of Groningen, 9700 RB Groningen, The Netherlands, {dagger} The Jackson Laboratory, Bar Harbor, Maine, 04609 and {ddagger} Novartis Institutes for BioMedical Research, East Hanover, New Jersey 07936

1 Corresponding author: The Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609.
E-mail: ron.korstanje{at}jax.org

We investigated the effect of apolipoprotein E (Apoe) on albuminuria in the males of two independent F2 intercrosses between C57BL/6J and A/J mice, using wild-type inbred strains in the first cross and B6-Apoe–/– animals in the second cross. In the first cross, we identified three quantitative trait loci (QTL): chromosome (Chr) 2 [LOD 3.5, peak at 70 cM, confidence interval (C.I.) 28–88 cM]; Chr 9 (LOD 2.0, peak 5 cM, C.I. 5–25 cM); and Chr 19 (LOD 1.9, peak 49 cM, C.I. 23–54 cM). The Chr 2 and Chr 19 QTL were concordant with previously found QTL for renal damage in rat and human. The Chr 9 QTL was concordant with a locus found in rat. The second cross, testing only Apoe–/– progeny, did not identify any of these loci, but detected two other loci on Chr 4 (LOD 3.2, peak 54 cM, C.I. 29–73 cM) and Chr 6 (LOD 2.6, peak 33 cM, C.I. 11–61 cM), one of which was concordant with a QTL found in rat. The dependence of QTL detection on the presence of Apoe and the concordance of these QTL with rat and human kidney disease QTL suggest that Apoe plays a role in renal damage.