Pnlip encoding pancreatic lipase is possible candidate for obesity QTL in the OLETF rat.
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 approximately 10-cM genomic region between D1Rat166 and D1Rat90 on chromosome 1 in (OLETF x 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 approximately 2.3-cM genomic region between D1Rat225 and D1Rat90, using informative recombinants selected from (Nidd6/of congenic x F344) F1 x Nidd6/of congenic backcross progenies. Among 46 genes located within the approximately 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 x F344) F1 x Nidd6/of congenic backcross progenies. These results suggest that Pnlip is possible candidate for the Nidd6/of QTL.
Muramatsu
Youji
Y
Department of Food Sciences, Shizuoka Eiwa Gakuin University Junior College, Ikeda, Shizuoka 422-8005, Japan.
Yamada
Takahisa
T
Taniguchi
Yukio
Y
Ogino
Tomoe
T
Kose
Hiroyuki
H
Matsumoto
Kozo
K
Sasaki
Yoshiyuki
Y
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D008049:Lipase / Q000235:genetics*; D018598:Minisatellite Repeats; D009765:Obesity / Q000201:enzymology / Q000235:genetics*; D010179:Pancreas / Q000201:enzymology*; D011110:Polymorphism, Genetic; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats
D017931:DNA Primers; D012333:RNA, Messenger; D008049:Lipase