Shin M K, Russell L B, Tilghman S M
Howard Hughes Medical Institute and Department of Molecular Biology, Princeton University, NJ 08544, USA.
Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13105-10. doi: 10.1073/pnas.94.24.13105.
The piebald locus on mouse chromosome 14 encodes the endothelin-B receptor (EDNRB), a G protein-coupled, seven-transmembrane domain protein, which is required for neural crest-derived melanocyte and enteric neuron development. A spontaneous null allele of Ednrb results in homozygous mice that are predominantly white and die as juveniles from megacolon. To identify the important domains for EDNRB function, four recessive juvenile lethal alleles created by either radiation or chemical mutagens (Ednrb27Pub, Ednrb17FrS, Ednrb1Chlc, and Ednrb3Chlo) were examined at the molecular level. Ednrb27Pub mice harbor a mutation at a critical proline residue in the fifth transmembrane domain of the EDNRB protein. A gross genomic alteration within the Ednrb gene in Ednrb3Chlo results in the production of aberrantly sized transcripts and no authentic Ednrb mRNA. Ednrb17FrS mice exhibited a decreased level of Ednrb mRNA, supporting previous observations that the degree of spotting in piebald mice is dependent on the amount of EDNRB expressed. Finally, no molecular defect was detected in Ednrb1Chlc mice, which produce normal levels of Ednrb mRNA in adult brain, suggesting that the mutation affects important regulatory elements that mediate the expression of the gene during development.
小鼠14号染色体上的花斑基因座编码内皮素-B受体（EDNRB），它是一种G蛋白偶联的七跨膜结构域蛋白，是神经嵴衍生的黑素细胞和肠神经元发育所必需的。Ednrb的一个自发无效等位基因导致纯合小鼠主要为白色，并在幼年时死于巨结肠。为了确定EDNRB功能的重要结构域，对由辐射或化学诱变剂产生的四个隐性幼年致死等位基因（Ednrb27Pub、Ednrb17FrS、Ednrb1Chlc和Ednrb3Chlo）进行了分子水平的检测。Ednrb27Pub小鼠在EDNRB蛋白的第五跨膜结构域的一个关键脯氨酸残基处发生了突变。Ednrb3Chlo中Ednrb基因的一个总体基因组改变导致产生大小异常的转录本，且没有真实的Ednrb mRNA。Ednrb17FrS小鼠的Ednrb mRNA水平降低，支持了之前的观察结果，即花斑小鼠的斑点程度取决于所表达的EDNRB的量。最后，在Ednrb1Chlc小鼠中未检测到分子缺陷，该小鼠在成年大脑中产生正常水平的Ednrb mRNA，这表明该突变影响了在发育过程中介导该基因表达的重要调控元件。
