title: An interval of the obesity QTL Nob3.38 within a QTL hotspot on chromosome 1 modulates behavioral phenotypes.
abstract: A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0-177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains.
authors: Departments of Pharmacology, Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors: Heike
authors: H
authors: Vogel
authors: Dirk
authors: D
authors: Montag
authors: Timo
authors: T
authors: Kanzleiter
authors: Wenke
authors: W
authors: Jonas
authors: Daniela
authors: D
authors: Matzke
authors: Stephan
authors: S
authors: Scherneck
authors: Alexandra
authors: A
authors: Chadt
authors: Jonas
authors: J
authors: Töle
authors: Reinhart
authors: R
authors: Kluge
authors: Hans-Georg
authors: HG
authors: Joost
authors: Annette
authors: A
authors: Schürmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001835:Body Weight; D033481:Chromosomes, Mammalian / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D040641:Quantitative Trait Loci
chemical_list: C092537:Ifi202b protein, mouse; D047908:Intracellular Signaling Peptides and Proteins