Pnlip encoding pancreatic lipase is possible candidate for obesity QTL in the OLETF rat

Y Muramatsu, T Yamada, Y Taniguchi, T Ogino… - Biochemical and …, 2005 - Elsevier
Y Muramatsu, T Yamada, Y Taniguchi, T Ogino, H Kose, K Matsumoto, Y Sasaki
Biochemical and biophysical research communications, 2005Elsevier
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∼ 10-cM genomic region between D1Rat166 and D1Rat90 on
chromosome 1 in (OLETF× 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 …
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 ∼10-cM genomic region between D1Rat166 and D1Rat90 on chromosome 1 in (OLETF×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 ∼2.3-cM genomic region between D1Rat225 and D1Rat90, using informative recombinants selected from (Nidd6/of congenic×F344) F1×Nidd6/of congenic backcross progenies. Among 46 genes located within the ∼ 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 5′-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×F344) F1×Nidd6/of congenic backcross progenies. These results suggest that Pnlip is possible candidate for the Nidd6/of QTL.
Elsevier