title: Dissection of a genetically complex cluster of growth and obesity QTLs on mouse chromosome 2 using subcongenic intercrosses.
abstract: In a previous study we characterized the B6.CAST-(D2Mit329-D2Mit457)N(6) (B62D) congenic strain, which possesses CAST/EiJ (CAST) chromosome 2 donor alleles from 74 to 180 Mbp on a C57BL6/J (B6) background. This strain exhibited significant decreases in body weight and adiposity attributable to the weight gain 2 (Wg2) quantitative trait locus (QTL). To refine the location of Wg2, we used a two-stage genetic dissection strategy consisting of a B62D x B6 backcross, which mapped Wg2 to the proximal portion of the B62D donor region, followed by the development of seven overlapping subcongenic F(2) intercrosses targeting the Wg2 genomic interval. Surprisingly, five of the seven intercrosses displayed significant differences, dependent on genotype, in body weight and/or fat pad mass. These effects were the result of at least four independent QTLs that were named Wg2a, b, c, and d. In contrast to the lean and low body weight phenotype of the B62D parental strain, mice homozygous for CAST congenic alleles (cast/cast) at Wg2a were significantly heavier at 6 and 9 weeks of age, while cast/cast mice at Wg2c had higher levels of total fat. Consistent with the prior observed effects of Wg2, cast/cast mice at Wg2b displayed significant decreases in 6- and 9-week body weight as well as a decrease in total fat pad mass. All of the QTLs had additive effects on body composition except Wg2d, which displayed underdominance for total fat mass. Significant differences in weight and adiposity were also observed in genetically identical b6/b6 homozygous mice across the panel of subcongenics, suggesting either maternal or paternal contributions to body composition. These data represent a significant advancement toward the identification of mouse chromosome 2 growth and obesity quantitative trait genes.
authors: Department of Animal Science, University of California Davis, Davis, CA 95616-8521, USA.
authors: Charles R
authors: CR
authors: Farber
authors: Juan F
authors: JF
authors: Medrano
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D003433:Crosses, Genetic; D003598:Cytoskeletal Proteins; D005838:Genotype; D006128:Growth / Q000235:genetics*; D006801:Humans; D007178:Inbreeding; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D005810:Multigene Family; D009765:Obesity / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*
chemical_list: D003598:Cytoskeletal Proteins; C505599:Erc2 protein, mouse
references: Genomics. 2001 Mar 1;72(2):209-12
references: 11401434
references: Gene. 2002 Oct 16;299(1-2):153-63
references: 12459263
references: Physiol Genomics. 2005 May 11;21(3):411-22
references: 15769905
references: J Immunol. 1998 Feb 1;160(3):1472-8
references: 9570569
references: Genetics. 2006 Jun;173(2):943-51
references: 16624897
references: J Lipid Res. 2005 Aug;46(8):1692-702
references: 15897602
references: Mamm Genome. 2004 Jun;15(6):460-71
references: 15181538
references: Heredity (Edinb). 2002 Oct;89(4):300-10
references: 12242647
references: BMC Genomics. 2006 May 02;7:102
references: 16670015
references: Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1928-34
references: 15331434
references: Genetics. 1989 Jan;121(1):185-99
references: 2563713
references: Mamm Genome. 2004 Jun;15(6):452-9
references: 15181537
references: Nucleic Acids Res. 2003 Jan 1;31(1):51-4
references: 12519945
references: Nature. 1996 Mar 14;380(6570):149-52
references: 8600386
references: J Bone Miner Res. 2006 Jan;21(1):97-104
references: 16355278
references: Diabetes. 2006 Aug;55(8):2265-71
references: 16873689
references: Obes Res. 2004 Sep;12(9):1408-20
references: 15483205
references: Bioinformatics. 2003 May 1;19(7):889-90
references: 12724300
references: Behav Genet. 1997 Jul;27(4):325-51
references: 9519560
references: Biometrics. 1987 Dec;43(4):913-28
references: 3427176
references: Diabetes. 2005 May;54(5):1603-6
references: 15855353
references: Obes Rev. 2005 Feb;6(1):5-7
references: 15655032
references: Mamm Genome. 2006 Jan;17(1):22-36
references: 16416088
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: Genetics. 1994 Nov;138(3):963-71
references: 7851788
references: Genet Res. 1984 Dec;44(3):293-308
references: 6530139
references: Genetics. 2007 Jan;175(1):349-60
references: 17110492
references: Int J Obes Relat Metab Disord. 2004 Feb;28(2):199-210
references: 14569280
references: Immunity. 2000 Jul;13(1):107-15
references: 10933399