title: Molecular and phenotypic analysis of Attractin mutant mice.
abstract: Mutations of the mouse Attractin (Atrn; formerly mahogany) gene were originally recognized because they suppress Agouti pigment type switching. More recently, effects independent of Agouti have been recognized: mice homozygous for the Atrn(mg-3J) allele are resistant to diet-induced obesity and also develop abnormal myelination and vacuolation in the central nervous system. To better understand the pathophysiology and relationship of these pleiotropic effects, we further characterized the molecular abnormalities responsible for two additional Atrn alleles, Atrn(mg) and Atrn(mg-L), and examined in parallel the phenotypes of homozygous and compound heterozygous animals. We find that the three alleles have similar effects on pigmentation and neurodegeneration, with a relative severity of Atrn(mg-3J) > Atrn(mg) > Atrn(mg-L), which also corresponds to the effects of the three alleles on levels of normal Atrn mRNA. Animals homozygous for Atrn(mg-3J) or Atrn(mg), but not Atrn(mg-L), show reduced body weight, reduced adiposity, and increased locomotor activity, all in the presence of normal food intake. These results confirm that the mechanism responsible for the neuropathological alteration is a loss--rather than gain--of function, indicate that abnormal body weight in Atrn mutant mice is caused by a central process leading to increased energy expenditure, and demonstrate that pigmentation is more sensitive to levels of Atrn mRNA than are nonpigmentary phenotypes.
authors.affiliation: Department of Pediatrics and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Gunn
authors.forename: T
authors.initials: T
authors.lastname: Inui
authors.forename: K
authors.initials: K
authors.lastname: Kitada
authors.forename: S
authors.initials: S
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: D M
authors.initials: DM
authors.lastname: Bouley
authors.forename: T
authors.initials: T
authors.lastname: Serikawa
authors.forename: G S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D000367:Age Factors; D054366:Agouti Signaling Protein; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005838:Genotype; D006720:Homozygote; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins / Q000737:chemistry; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D010858:Pigmentation / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D054366:Agouti Signaling Protein; C117928:Atrn protein, mouse; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D008543:Melanins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger