A model for obesity and gigantism due to disruption of the Ankrd26 gene.
Obesity is a major health hazard that is caused by a combination of genetic and behavioral factors. Several models of obesity have been described in mice that have defects in the production of peptide hormones, in the function of cell membrane receptors, or in a transcription factor required for neuronal cell development. We have been investigating the function of a family of genes (POTE and ANKRD26) that encode proteins that are associated with the inner aspect of the cell membrane and that contain both ankyrin repeats and spectrin helices, motifs known to interact with signaling proteins in the cell. To assess the function of ANKRD26, we prepared a mutant mouse with partial inactivation of the Ankrd26 gene. We find that the homozygous mutant mice develop extreme obesity, insulin resistance, and an increase in body size. The obesity is associated with hyperphagia with no reduction in energy expenditure and activity. The Ankrd26 protein is expressed in the arcuate and ventromedial nuclei within the hypothalamus and in the ependyma and the circumventricular organs that act as an interface between the peripheral circulation and the brain. In the enlarged hearts of the mutant mice, the levels of both phospho-Akt and mTOR were elevated. These results show that alterations in an unidentified gene can lead to obesity and identify a molecular target for the treatment of obesity.
Bera
Tapan K
TK
Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4264, USA.
Liu
Xiu-Fen
XF
Yamada
Masanori
M
Gavrilova
Oksana
O
Mezey
Eva
E
Tessarollo
Lino
L
Anver
Miriam
M
Hahn
Yoonsoo
Y
Lee
Byungkook
B
Pastan
Ira
I
D000818:Animals; D049628:Body Size; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D005091:Exons; D020224:Expressed Sequence Tags; D005838:Genotype; D005877:Gigantism / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D009154:Mutation; D009765:Obesity / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
C526207:Ankrd26 protein, mouse; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors