GENETIC INTERACTIONS COORDINATING PIEBALD SPOTTING Pavan, W

在花斑鼠(S)身上观察到的黑白斑点图案是由于内皮素受体B突变导致的神经脊发育异常所致。在两个携带S突变的近交系菌株(梅耶斯/S和C3H S/S)中，色素图案的严重程度和分布非常不同。我们假设，其他基因可能负责协调观察到的图案差异。对这两个品系的回交后代的定量遗传分析发现，有4个遗传修饰基因位于第2、5、8和10号染色体上。第10染色体上的修饰基因使背部斑点的数量增加了2倍(19.7%比9.1%，p&lt；0.0001)，这表明该修饰基因对色素的形成有空间或时间上的影响。对作图数据的分析表明，Steel(肥大细胞生长因子)是该基因座的候选基因。两个分离株的序列比较没有发现编码区的差异，但Northern印迹分析发现成虫组织中稳定状态的mRNA水平存在差异。对Steel基因基因组结构的比较表明，12/12限制性内切酶的片段大小存在差异，而两个未连锁的基因EDNRB和ET-3没有差异。这些结果表明，在S小鼠的迈耶品系中观察到的背部斑点增加是由于突变改变了Steel的表达模式。我们使用迈耶品系和Steel缺失小鼠的杂交来验证这一假设。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。未来还将探索利用胚胎重建实验和表达模式研究来确定每个修饰基因座的分子变化和相互作用。-生物技术研究、癌症研究、消化系统疾病、基因图谱(非人类)、神经科学、儿科研究、

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. - biotechnology research, cancer research, digestive diseases, gene mapping(non-human), neuroscience, pediatric research,