A candidate gene for the mouse mutation tubby

被引:274
作者
NobenTrauth, K
Naggert, JK
North, MA
Nishina, PM
机构
[1] JACKSON LAB,BAR HARBOR,ME 04609
[2] SEQUANA THERAPEUT INC,LA JOLLA,CA 92037
关键词
D O I
10.1038/380534a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
A MUTATION in the tub gene causes maturity-onset obesity, insulin resistance(1), and sensory (d)eficits(2,3). In contrast to the rapid juvenile-onset weight gain seen in diabetes (db) and obese (ob) mice, obesity in tubby mice develops gradually, and strongly resembles the late-onset obesity seen in the human population. Excessive deposition of adipose tissue eventually leads to a twofold increase of body weight. Tubby mice also suffer retinal degeneration and neurosensory hearing loss(2,3). The tripartite character of the tubby phenotype shows striking similarity to human obesity syndromes, such as Alstrom(4) and Bardet-Biedl(5). Here we report the identification of a G --> T transversion in a candidate gene that abolishes a donor splice site in the 3' coding region and results in a larger transcript containing the unspliced intron. This alteration is predicted to replate the 44-carboxy-terminal amino acids with a 20-amino-acid sequence not found in the wild-type protein. Additionally, a second, prematurely truncated transcript with the unspliced intron is observed in testis messenger RNA and a 2-3-fold increase in brain mRNA is observed in tubby mice compared to B6. The phenotypic features of tubby mice may be the result of cellular apoptosis triggered by expression of the mutated tub gene.
引用
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页码:534 / 538
页数:5
相关论文
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