title: Dissection of multigenic obesity traits in congenic mouse strains.
abstract: Previous quantitative trait locus mapping (QTL) identified multigenic obesity (MOB) loci on mouse Chromosome (Chr) 2 that influence the interrelated phenotypes of obesity, insulin resistance, and dyslipidemia. To better localize and characterize the MOB locus, three congenic mouse strains were created. Overlapping genomic intervals from the lean CAST/Ei (CAST) strain were introgressed onto an obesity-susceptible C57BL/6 (BL6) background to create proximal (15 Mb-73 Mb), middle (63 Mb-165 Mb), and distal (83 Mb-182 Mb) congenic strains. The congenic strains showed differences in obesity, insulin, and lipid traits consistent with the original QTL analysis for the locus. Importantly, characterization of the MOB congenics localized the effects of genes that underlie obesity-related traits to an introgressed interval (73-83 Mb) unique to the middle MOB congenic. Conversely, significant differences between the lipid and insulin profiles of the middle and distal MOB congenics implicated the presence of at least two genes that underlie these traits. When fed an atherogenic diet, several traits associated with metabolic syndrome were observed in the distal MOB congenic, while alterations in plasma lipoproteins were observed in the middle MOB congenic strain.
authors.affiliation: Department of Human Genetics, Gonda/Goldschmeid Center for Neuroscience and Human Genetics Research, 695 Charles E Young Dr South, Room 6524, Los Angeles, CA 90095-7088, USA. destrada@mednet.ucla.edu
authors.forename: Daria
authors.initials: D
authors.lastname: Estrada-Smith
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Castellani
authors.forename: Howard
authors.initials: H
authors.lastname: Wong
authors.forename: Ping-Zi
authors.initials: PZ
authors.lastname: Wen
authors.forename: Aileen
authors.initials: A
authors.lastname: Chui
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Richard C
authors.initials: RC
authors.lastname: Davis
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000235:genetics*; D002784:Cholesterol / Q000378:metabolism; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D003433:Crosses, Genetic; D005819:Genetic Markers; D007333:Insulin Resistance / Q000235:genetics*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051379:Mice; D020297:Mice, Congenic / Q000235:genetics*; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D019655:Quantitative Trait, Heritable
chemical_list: D005819:Genetic Markers; D008074:Lipoproteins; D002784:Cholesterol