DEFICIENCY OF THE BETA-3 SUBUNIT OF THE TYPE-A GAMMA-AMINOBUTYRIC-ACID RECEPTOR CAUSES CLEFT-PALATE IN MICE

In addition to its function in the nervous system gamma-aminobutyric a cid (GABA) has been implicated in mouse craniofacial development by th e results of both teratological(1-3), and genetic studies(4). We previ ously reported that disruption of the cleft palate 1 (cp1) locus, clos ely 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(4). We proposed that t he beta 3 subunit gene (Gabrb3) of the GABA(A) receptor might be a can didate for cp1 (ref. 4); our earlier studies(4,5) had localized cp1 to an interval beginning distal to the gene for the GABA(A) receptor alp ha 5 subunit (Gabra5) and ending within the Gabrb3 coding region. To t est the hypothesis that deletion of Gabrb3, and not another gene in th e interval, causes CP, we performed an experiment to rescue the CP phe notype by introducing a Gabrb3 transgene into p(4THO-II) homozygotes. We now show that such transgenic mice are phenotypically normal, indic ating that Gabrb3 is indeed the cp1 locus.