Y. Nakatsu et al., A CLUSTER OF 3 GABA(A) RECEPTOR SUBUNIT GENES IS DELETED IN A NEUROLOGICAL MUTANT OF THE MOUSE P-LOCUS, Nature, 364(6436), 1993, pp. 448-450
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 tre
mor and jerky gait2. We report here that the genes encoding the gamma-
aminobutyric acid type A (GABA(A)) receptor subunits alpha5 (originall
y described as alpha4; ref. 4), beta3 and gamma3 are disrupted by a de
letion in p(cp) mice. We also show that the alpha5 and gamma3 genes ar
e located between the p and beta3 genes on mouse chromosome 7. The p(c
p) 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) mic
e may be useful in defining the region containing the gene(s) for this
syndrome.