Mercer J A, Seperack P K, Strobel M C, Copeland N G, Jenkins N A
Mammalian Genetics Laboratory, NCI-Frederick Cancer Research and Development Center, Maryland 21702.
Nature. 1991 Feb 21;349(6311):709-13. doi: 10.1038/349709a0.
Hundreds of murine dilute mutations have been identified and analysed, making dilute one of the best genetically characterized of all mammalian loci. The recessive dilute (d) coat colour mutation carried by many inbred strains of mice produces a lightening of coat colour, caused by an abnormal adendritic melanocyte morphology that results in an uneven release of pigment granules into the developing hair shaft. Most dilute alleles (dilute-lethal) also produce a neurological defect, characterized by convulsions and opisthotonus, apparent at 8-10 days of age and continuing until the death of the animal at 2-3 weeks of age. The discovery that the original dilute allele (now termed dilute-viral or dV) is the result of the integration of an ecotropic murine leukaemia provirus has allowed the cloning of genomic DNA and in this study complementary DNA, from the dilute locus. The predicted dilute amino-acid sequence indicates that dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (alpha-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed in both embryonic and adult tissues and are very abundant in neurons of the central nervous system, cephalic ganglia, and spinal ganglia. These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons.
已经鉴定并分析了数百种小鼠稀释突变，使稀释成为所有哺乳动物基因座中遗传特征最明确的基因座之一。许多近交系小鼠携带的隐性稀释（d）毛色突变会导致毛色变浅，这是由异常的无树突黑素细胞形态引起的，这种形态会导致色素颗粒不均匀地释放到发育中的毛干中。大多数稀释等位基因（稀释致死）还会产生神经缺陷，其特征为惊厥和角弓反张，在8至10日龄时明显出现，并持续到动物在2至3周龄时死亡。最初的稀释等位基因（现称为稀释病毒或dV）是嗜亲性小鼠白血病前病毒整合的结果，这一发现使得能够从稀释基因座克隆基因组DNA以及在本研究中克隆互补DNA。预测的稀释氨基酸序列表明，稀释编码一种新型的肌球蛋白重链，其尾部或C末端区域同时具有II型（α螺旋卷曲螺旋）和I型（非卷曲螺旋）肌球蛋白重链的元件。稀释转录本在胚胎和成年组织中差异表达，并且在中枢神经系统、头神经节和脊髓神经节的神经元中非常丰富。这些结果表明稀释基因产物在黑素细胞和神经元的细胞突起的形成、维持或功能中起重要作用。
