Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10770448 | Biochemical and Biophysical Research Communications | 2005 | 7 Pages |
Abstract
The Otsuka Long-Evans Tokushima Fatty (OLETF) rat exhibits polygenic obesity, and one of quantitative trait loci (QTLs) responsible for a susceptibility to obesity in the OLETF, Nidd6/of, has been mapped to the â¼10-cM genomic region between D1Rat166 and D1Rat90 on chromosome 1 in (OLETF Ã normal) F2 intercross. In this study, we have attempted to identify the causal gene for the Nidd6/of QTL. A Nidd6/of congenic strain, constructed by introgressing the OLETF allele on the mapped Nidd6/of region in the normal F344 rat strain, confirmed the existence of the Nidd6/of as obesity QTL. The Nidd6/of region was refined to a â¼2.3-cM genomic region between D1Rat225 and D1Rat90, using informative recombinants selected from (Nidd6/of congenic Ã F344) F1 Ã Nidd6/of congenic backcross progenies. Among 46 genes located within the â¼ 2.3-cM region, pancreatic lipase gene, Pnlip, was regarded as the most prominent and physiologically relevant positional candidate for the Nidd6/of QTL. We found that Pnlip possesses an OLETF allele-specific increase of mRNA levels in the pancreas, and that the OLETF allele is longer in variable number of tandem repeat (VNTR) within the 5â²-flanking region than normal alleles. We further showed that the Nidd6/of QTL completely cosegregates with Pnlip VNTR in the informative recombinants from (Nidd6/of congenic Ã F344) F1 Ã Nidd6/of congenic backcross progenies. These results suggest that Pnlip is possible candidate for the Nidd6/of QTL.
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Authors
Youji Muramatsu, Takahisa Yamada, Yukio Taniguchi, Tomoe Ogino, Hiroyuki Kose, Kozo Matsumoto, Yoshiyuki Sasaki,