Quantitative trait loci for urinary albumin in crosses between C57BL/6J and A/J inbred mice in the presence and absence of Apoe.
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.
Doorenbos
Carolien
C
Department of Internal Medicine, Division of Medical Biology, University Medical Centre, University of Groningen, 9700 RB Groningen, The Netherlands.
Tsaih
Shirng-Wern
SW
Sheehan
Susan
S
Ishimori
Naoki
N
Navis
Gerjan
G
Churchill
Gary
G
Dipetrillo
Keith
K
Korstanje
Ron
R
D000419:Albuminuria / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D003433:Crosses, Genetic; D005838:Genotype; D008126:Lod Score; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D040641:Quantitative Trait Loci / Q000235:genetics*
D001057:Apolipoproteins E