GENETIC INTERACTIONS COORDINATING PIEBALD SPOTTING

观察到的黑白斑点图案 花斑(S)小鼠神经脊发育异常 由于内皮素受体B(EDNRB)的突变。严重程度 而色素图案的分布在两种情况下是非常不同的 携带S突变的近交系(梅耶斯/S和C3H S/S)。我们 假设额外的基因可能负责 协调观察到的图案差异。量化 这两个品系回交后代的遗传分析 鉴定了位于第2、5、8号染色体上的四个遗传修饰物 和10.10号染色体上的修饰物增加了背部 斑点比腹点多2倍(19.7%vs9.1%，p&lt； 0.0001)，表明此修饰符在空间或时间上对 颜料图案。映射数据涉及钢(桅杆)的分析 细胞生长因子)作为该基因座的候选基因。数列 对cdna分离株的比较没有表明在 编码区，但稳定状态水平的差异 Northern印迹法检测成体组织中的mRNA表达。 钢基因的基因组结构比较 12/12限制性内切酶显示出不同的 DNA片段的大小，但没有观察到差异 两个未连接的基因，EDNRB和内皮素3。这些结果 提示在Mayer品系中观察到的背部斑点增加 S小鼠的死亡是由于一种突变改变了钢的表达 模式。我们已经通过使用 迈耶品系和钢零小鼠。与我们的假设一致， Steel的Mayer等位基因不能补充Steel的零突变 并导致背部斑点增加。未来的研究使用 胚胎重建实验及表达模式 还将探索确定分子变化的研究 以及在每个修改器位置的相互作用。

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 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 un-linked 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.