Ikeda Akihiro, Naggert Jürgen K, Nishina Patsy M
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
Exp Eye Res. 2002 Apr;74(4):455-61. doi: 10.1006/exer.2001.1139.
Mice that carry the recessive mutation tub develop neurosensory defects including retinal and cochlear degeneration, as well as maturity-onset obesity associated with insulin resistance. The biological function of the gene and the mechanism by which it induces its phenotypes are still unclear. In order to elucidate the pathways through which tub functions, in the current study, QTL modifiers were identified in an F2 intercross between (C57BL/6J- tub/tub and AKR/J-+/+) F1 hybrids (AKR intercross). The thickness of the outer nuclear layer of the retina and the number of photoreceptor nuclei were assessed in F2 mice homozygous for the tub mutation. A genome-wide scan revealed a significant linkage on chromosome 11 (named motr1) and two suggestive linkages on chromosomes 2 and 8. Interestingly, the same chromosome 2 region identified for the hearing modifier of tubby, the moth1 locus, showed a peak lod score of 2.3 for protection from retinal degeneration. This result suggests that the gene responsible for the QTL on chromosome 2 might be involved in a common pathway through which retinal and cochlear degeneration are induced in tubby mice.
携带隐性突变tub的小鼠会出现神经感觉缺陷，包括视网膜和耳蜗退化，以及与胰岛素抵抗相关的成年期肥胖。该基因的生物学功能及其诱导表型的机制仍不清楚。为了阐明tub发挥作用的途径，在本研究中，在（C57BL/6J - tub/tub和AKR/J - +/+）F1杂种（AKR杂交）之间的F2杂交中鉴定了QTL修饰基因。在纯合tub突变的F2小鼠中评估了视网膜外核层的厚度和光感受器细胞核的数量。全基因组扫描显示在11号染色体上有一个显著的连锁（命名为motr1），在2号和8号染色体上有两个提示性的连锁。有趣的是，为tubby的听力修饰基因鉴定的相同的2号染色体区域，即moth1位点，在预防视网膜退化方面显示出2.3的最高对数优势分数。这一结果表明，2号染色体上负责QTL的基因可能参与了tubby小鼠中诱导视网膜和耳蜗退化的共同途径。
