Genetic analysis of attractin homologs.
Attractin (ATRN) and Attractin-like 1 (ATRNL1) are highly similar type I transmembrane proteins. Atrn null mutant mice have a pleiotropic phenotype including dark fur, juvenile-onset spongiform neurodegeneration, hypomyelination, tremor, and reduced body weight and adiposity, implicating ATRN in numerous biological processes. Bioinformatic analysis indicated that Atrn and Atrnl1 arose from a common ancestral gene early in vertebrate evolution. To investigate the genetics of the ATRN system and explore potential redundancy between Atrn and Atrnl1, we generated and characterized Atrnl1 loss- and gain-of-function mutations in mice. Atrnl1 mutant mice were grossly normal with no alterations of pigmentation, central nervous system pathology or body weight. Atrn null mutant mice carrying a beta-actin promoter-driven Atrnl1 transgene had normal, agouti-banded hairs and significantly delayed onset of spongiform neurodegeneration, indicating that over-expression of ATRNL1 compensates for loss of ATRN. Thus, the two genes are redundant from the perspective of gain-of-function but not loss-of-function mutations.
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
Will P
WP
Walker
Swaroop
S
Aradhya
Che-Lin
CL
Hu
Shiliang
S
Shen
Wei
W
Zhang
Arezou
A
Azarani
XinYun
X
Lu
Gregory S
GS
Barsh
Teresa M
TM
Gunn
D048868:Adaptor Proteins, Signal Transducing / Q000145:classification* / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000145:classification* / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D010858:Pigmentation / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C117928:Atrn protein, mouse; C480020:Atrnl1 protein, mouse; D008565:Membrane Proteins