Pnlip encoding pancreatic lipase is possible candidate for obesity QTL in the OLETF rat.
Pnlip encoding pancreatic lipase is possible candidate for obesity QTL in the OLETF rat.
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DOI：
10.1016/j.bbrc.2005.04.040
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发表时间：
2005-06
影响因子：
3.1
通讯作者：
Y. Muramatsu;Takahisa Yamada;Y. Taniguchi;T. Ogino;H. Kose;Kozo Matsumoto;Y. Sasaki
中科院分区：
文献类型：
--
作者：
Y. Muramatsu;Takahisa Yamada;Y. Taniguchi;T. Ogino;H. Kose;Kozo Matsumoto;Y. Sasaki
大冢长埃文斯德岛肥胖大鼠（OLETF）是一个多基因肥胖病易感性QTLs，在（OLETF×正常）F2代杂交中，Nidd 6/of定位于1号染色体D1 Rat 166和D1 Rat 90之间的约10 cM基因组区域。在这项研究中，我们试图鉴定QTL的Nidd 6/的因果基因。通过在正常F344大鼠品系中定位的Nidd 6/of区域上渐渗OLETF等位基因构建的Nidd 6/of同源品系证实了Nidd 6/of作为肥胖QTL的存在。利用从（Nidd 6/of同基因组×F344）F1× Nidd 6/of同基因组回交后代中筛选出的信息重组子，将Nidd 6/of基因组区域精确到D1 Rat 225和D1 Rat 90之间的约2.3cM基因组区域。在位于Nidd 6/2.3-cM区域的46个基因中，胰脂肪酶基因Pnlip被认为是Nidd 6/2.3-cM区域内最突出的生理相关的位置候选者。我们发现Pnlip具有OLETF等位基因特异性的胰腺mRNA水平的增加，并且OLETF等位基因在5′-侧翼区域内的可变数目串联重复（VNTR）比正常等位基因长。在（Nidd 6/×F344）F1× Nidd 6/回交后代的重组信息中，QTL的Nidd 6/与Pnlip VNTR完全共分离。这些结果表明Pnlip可能是Nidd 6/of QTL的候选基因。
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) F2intercross. 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.