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)。色素花纹的严重程度和分布 在两个携带S突变的近交系菌株中存在巨大差异 (发稿梅耶斯/S C3H S/S)我们假设额外的基因可能是 负责协调观察到的图案差异。 这两个品系回交后代的数量遗传分析 确定了位于第2、5、8和10号染色体上的四个遗传修饰物。 10号染色体上的修饰者将背部斑点增加2倍以上。 而不是腹面斑点(19.7%比9.1%，p&lt；0.0001)，这表明 修饰剂对颜料图案化有空间或时间影响。分析 10号染色体上的修饰物使背部斑点增加2倍 超过腹面斑点(19.7%比9.1%，p&lt；0.0001)，表明这一点 修饰剂对颜料图案化有空间或时间影响。分析 映射数据的影响将Steel(肥大细胞生长因子)作为候选 这个基因座的基因。Cdna分离株的序列比较没有。 指示编码区中的任何差异，但 Northern印迹法观察成体组织中稳态基因的表达水平 分析。钢基因的基因组结构比较 显示大小不同的12/12限制性内切酶 然而，在未链接的两个DNA片段中没有观察到差异 基因，EDNRB和内皮素3。这些结果表明背部 在S小鼠的迈耶品系中观察到的斑点是由于 改变钢的表达模式。我们已经通过以下方式验证了这一假设 使用Mayer品系和Steel Null小鼠之间的杂交。一致 在我们的假设下，钢铁公司的迈耶等位基因不能补充钢铁公司 零突变，并导致背部斑点增加。未来研究 利用胚胎重建实验和表达模式研究 也将被探索以确定分子变化和 每个修改器轨迹处的交互作用。

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 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. Comparison of the genomic structure of the Steel gene demonstrated 12/12 restriction enzymes showing differences in the size of DNA fragments, however no differences were observed in two unlinked genes, EDNRB and endothelin 3. 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. We have tested this hypothesis by using crosses between the Mayer strain and Steel null mice. Consistent with our hypothesis, the Mayer allele at Steel cannot complement a Steel null mutation and results in increased dorsal spotting. Future studies using embryonic reconstitution experiments and expression pattern studies will also be explored to determine the molecular alterations and interactions at each modifier locus.