A CLUSTER OF 3 GABA(A) RECEPTOR SUBUNIT GENES IS DELETED IN A NEUROLOGICAL MUTANT OF THE MOUSE P-LOCUS

THE mouse pink-eyed cleft-palate (p(cp)) mutation is characterized by hypopigmentation associated with cleft palate, neurological disorders and runting1,2. Most p(cp) homozygotes are born with cleft palate and die shortly after birth, presumably as a result of feeding problems3. A few exceptional p(cp) mutants live beyond this stage but display tremor and jerky gait2. We report here that the genes encoding the gamma-aminobutyric acid type A (GABA(A)) receptor subunits alpha5 (originally described as alpha4; ref. 4), beta3 and gamma3 are disrupted by a deletion in p(cp) mice. We also show that the alpha5 and gamma3 genes are located between the p and beta3 genes on mouse chromosome 7. The p(cp) deletion leads to alterations of binding properties of the GABA(A) receptors in the brain, providing an in vivo model system for studying GABA(A) receptor function. The human homologue of the region deleted in p(cp) mice is associated with Angelman syndrome5-9. Thus, p(cp) mice may be useful in defining the region containing the gene(s) for this syndrome.