Culiat C T, Stubbs L J, Woychik R P, Russell L B, Johnson D K, Rinchik E M
Biology Division, Oak Ridge National Laboratory, Tennessee 37831-8077, USA.
Nat Genet. 1995 Nov;11(3):344-6. doi: 10.1038/ng1195-344.
In addition to its function in the nervous system, gamma-aminobutyric acid (GABA) has been implicated in mouse craniofacial development by the results of both teratological, and genetic studies. We previously reported that disruption of the cleft palate 1 (cp1) locus, closely linked to the pink-eyed dilution (p) locus on mouse chromosome 7, causes a 95% penetrant, recessive, neonatally-lethal cleft palate (CP) in mice homozygous for the p(4THO-II) deletion. We proposed that the beta 3 subunit gene (Gabrb3) of the GABAA receptor might be a candidate for cp1 (ref. 4); our earlier studies had localized cp1 to an interval beginning distal to the gene for the GABAA receptor alpha 5 subunit (Gabra5) and ending within the Gabrb3 coding region. To test the hypothesis that deletion of Gabrb3, and not another gene in the interval, causes CP, we performed an experiment to rescue the CP phenotype by introducing a Gabrb3 transgene into p(4THO-II) homozygotes. We now show that such transgenic mice are phenotypically normal, indicating that Gabrb3 is indeed the cp1 locus.
除了在神经系统中的功能外，γ-氨基丁酸（GABA）已通过致畸学和遗传学研究结果被证明与小鼠颅面发育有关。我们之前报道，腭裂1（cp1）位点与小鼠7号染色体上的粉红眼稀释（p）位点紧密连锁，在纯合p（4THO-II）缺失的小鼠中，该位点的破坏会导致95%的显性、隐性、新生儿致死性腭裂（CP）。我们提出GABAA受体的β3亚基基因（Gabrb3）可能是cp1的候选基因（参考文献4）；我们早期的研究已将cp1定位到一个区间，该区间始于GABAA受体α5亚基（Gabra5）基因的远端，止于Gabrb3编码区内。为了验证是Gabrb3的缺失而非该区间内的其他基因导致CP这一假设，我们进行了一项实验，通过将Gabrb3转基因导入p（4THO-II）纯合子来挽救CP表型。我们现在表明，此类转基因小鼠在表型上是正常的，这表明Gabrb3确实是cp1位点。
