Nissenbaum Jonathan, Shpigler Hagai, Pisanté Anne, DelCanho Sonia, Minert Anne, Seltzer Ze'ev, Devor Marshall, Darvasi Ariel
Department of Genetics, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Pain. 2008 Mar;135(1-2):92-7. doi: 10.1016/j.pain.2007.05.006. Epub 2007 Jun 8.
We aimed to locate a chronic pain-associated QTL in the rat (Rattus norvegicus) based on previous findings of a QTL (pain1) on chromosome 15 of the mouse (Mus musculus). The work was based on rat selection lines HA (high autotomy) and LA (low autotomy) which show a contrasting pain phenotype in response to nerve injury in the neuroma model of neuropathic pain. An F(2) segregating population was generated from HA and LA animals. Phenotyped F(2) rats were genotyped on chromosome 7 and chromosome 2, regions that share a partial homology with mouse chromosome 15. Our interval mapping analysis revealed a LOD score value of 3.63 (corresponding to p=0.005 after correcting for multiple testing using permutations) on rat chromosome 2, which is suggestive of the presence of a QTL affecting the predisposition to neuropathic pain. This QTL was mapped to the 14-26cM interval of chromosome 2. Interestingly, this region is syntenic to mouse chromosome 13, rather than to the region of mouse chromosome 15 that contains pain1. This chromosomal position indicates that it is possibly a new QTL, and hence we name it pain2. Further work is needed to replicate and to uncover the underlying gene(s) in both species.
基于此前在小鼠（小家鼠）15号染色体上发现的一个数量性状基因座（pain1），我们旨在在大鼠（褐家鼠）中定位一个与慢性疼痛相关的数量性状基因座。这项工作基于大鼠选择系HA（高自切）和LA（低自切），它们在神经性疼痛的神经瘤模型中对神经损伤表现出相反的疼痛表型。从HA和LA动物中产生了一个F(2)分离群体。对具有表型的F(2)大鼠在7号染色体和2号染色体上进行基因分型，这两个区域与小鼠15号染色体存在部分同源性。我们的区间定位分析显示，在大鼠2号染色体上的LOD得分值为3.63（经置换法进行多重检验校正后对应p = 0.005），这表明存在一个影响神经性疼痛易感性的数量性状基因座。这个数量性状基因座被定位到2号染色体的14 - 26cM区间。有趣的是，这个区域与小鼠13号染色体同线，而不是与包含pain1的小鼠15号染色体区域同线。这个染色体位置表明它可能是一个新的数量性状基因座，因此我们将其命名为pain2。需要进一步开展工作以在两个物种中重复验证并揭示潜在的基因。
