GENETIC INTERACTIONS COORDINATING PIEBALD SPOTTING

花斑(S)小鼠的黑白斑点模式观察结果 由内皮素突变引起的神经脊发育异常 B受体(EDNRB)。色素的严重程度和分布 携带S的两个近交系的模式非常不同 突变(梅耶斯/S和C3H S/S)。我们假设额外的基因 可能负责协调图案化方面的差异 观察到的。这些回交后代的数量遗传分析 两个菌株鉴定出位于2号染色体上的四个遗传修饰物， 5、8和10。10号染色体上的修饰物增加了背部斑点 比腹面斑点多2倍(19.7%比9.1%，p&lt；0.0001)，这表明 此修改器对颜料图案化具有空间或时间影响。 对映射数据的分析暗示Steel(肥大细胞生长因子)为 该基因座的候选基因。不同分离株的序列比较 然而，没有表明编码区有任何差异 成体组织中稳态mRNA水平的差异是 通过Northern杂交分析观察到。这些结果表明， 在S小鼠的迈耶品系中观察到的背部斑点是由于 改变钢铁表达模式的突变。

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.