GENETIC INTERACTIONS COORDINATING PIEBALD SPOTTING

协调花斑斑点的遗传相互作用

• 批准号: 5203435
• 负责人: W PAVAN
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5203435
• 关键词: complementary DNA; developmental genetics; gene expression; gene interaction; gene mutation; genetic mapping; genetic strain; interleukin 3; laboratory mouse; messenger RNA; neural plate /tube; northern blottings; nucleic acid sequence; pigmentation; receptor expression

The black and white spotting pattern observed in piebald(s) mice results from abnormal neural crest development due to a mutation in endothelin receptor B (EDNRB). The severity and distribution of the pigment patterns are vastly different in two inbred strains carrying the s mutation (Mayers/s and C3H s/s). We hypothesized that additional genes may be responsible for coordinating the differences in patterning observed. Quantitative genetic analysis of backcross progeny from these two strains identified four genetic modifiers located on Chromosomes 2, 5, 8 and 10. The modifier on Chromosome 10 increases the dorsal spotting 2-fold more than ventral spotting (19.7% vs 9.1%, p < 0.0001), suggesting this modifier has spatial or temporal affects on pigment patterning. Analysis of mapping data implicates Steel (mast cell growth factor) as a candidate gene for this locus. Sequence comparison of cDNA isolates did not indicate any differences in the coding region, however differences in the level of steady state mRNA in adult tissues was observed by Northern blot analyses. These results suggest the increased dorsal spotting observed in the Mayer strain of s mice is due to a mutation that alters the Steel expression pattern.

在Piebald（S）小鼠中观察到的黑白斑点模式结果 由于内皮素突变引起的异常神经rest发育 受体B（EDNRB）。 色素的严重程度和分布 携带S的两个近交菌株中的图案大不相同 突变（Mayers/S和C3H S/S）。 我们假设其他基因 可能负责协调模式的差异 观察到。 从这些的后代后代的定量遗传分析 两种菌株鉴定出位于染色体2上的四个遗传修饰剂， 5、8和10。染色体10的修饰符增加了背斑 比腹侧斑点多2倍（19.7％vs 9.1％，p <0.0001），表明 该修饰符对色素模式具有空间或时间影响。 映射数据的分析涉及钢（肥大细胞生长因子） 该基因座的候选基因。 cDNA分离株的序列比较 没有表明编码区域有任何差异，但是 成人组织中稳态mRNA水平的差异为 通过北印迹分析观察到。 这些结果表明增加 在S小鼠的Mayer菌株中观察到的背侧斑点是由于A 改变钢表达模式的突变。