A cluster of three GABAA receptor subunit genes is deleted in a neurological mutant of the mouse p locus

Abstract

THE mouse pink-eyed cleft-palate (p^cp ) mutation is characterized by hypopigmentation associated with cleft palate, neurological disorders and runting^1,2. 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 γ-aminobutyric acid type A (GABA_A) receptor sub-units α5 (originally described as α4; ref. 4), β3 and γ3 are disrupted by a deletion in p^cp mice. We also show that the α5 and γ3 genes are located between the p and β3 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 syndrome^5–9. Thus, p^cp mice may be useful in defining the region containing the gene(s) for this syndrome.