NDLI: Identification of a mutation in ADD1/SREBP-1 in the spontaneously hypertensive rat

Content Provider	Springer Nature Link
Author	Pravenec, Michal Jansa, Petr Kostka, Vlastimil Zídek, Václav Křen, Vladimír Forejt, Jiří Kurtz, Theodore W.
Copyright Year	2001
Abstract	It has recently been proposed that primary mutations in genes involved in fatty acid and lipid metabolism may contribute to the pathogenesis of insulin resistance and dyslipidemia often observed in spontaneous forms of hypertension. In the current study in the spontaneously hypertensive rat (SHR), we mapped and sequenced the gene encoding a key transcription factor known as ADD1 (adipocyte determination and differentiation factor 1) or SREBP-1c (sterol regulatory element binding protein-1c) that has recently been identified as a master regulator of genes involved in the hepatic control of lipid and carbohydrate metabolism. We found that (1) the gene for ADD1/SREBP-1c maps to a region of rat Chromosome 10 previously reported to contain a quantitative trait locus involved in the regulation of hepatic cholesterol levels and (2) the SHR harbors a valine-to-methionine substitution in the COOH terminal portion of the ADD1/SREBP-1 protein that is not present in 44 other strains of laboratory rats. These findings, together with previous studies showing that transgenic expression of SREBP-1 isoforms has major effects on hepatic fatty acid and cholesterol biosynthesis, suggest that naturally occurring variation in the gene encoding the SREBP-1 isoforms might contribute to inherited variation in lipid metabolism in the SHR versus other strains of rats. These results should serve to motivate future transfection studies of the effect of the SHR mutant on SREBP-1 expression and activation in vitro, as well as the development of congenic and transgenic strains of SHR to investigate the effects of different variants of SREBP-1 on carbohydrate and lipid metabolism in vivo.
Starting Page	295
Ending Page	298
Page Count	4
File Format	PDF
ISSN	09388990
Journal	Mammalian Genome
Volume Number	12
Issue Number	4
e-ISSN	14321777
Language	English
Publisher	Springer-Verlag
Publisher Date	2001-02-27
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell Biology Anatomy Zoology
Content Type	Text
Resource Type	Article
Subject	Genetics

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