CLEFT-PALATE IN MICE WITH A TARGETED MUTATION IN THE GAMMA-AMINOBUTYRIC ACID-PRODUCING ENZYME GLUTAMIC-ACID DECARBOXYLASE-67

The functions of neurotransmitters in fetal development are poorly und erstood. Genetic observations have suggested a role for the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) in the nor mal development of the mouse palate. Mice homozygous for mutations in the beta-3 GABA(A) receptor subunit develop a cleft secondary palate. GABA, the ligand for this receptor, is synthesized by the enzyme gluta mic acid decarboxylase. We have disrupted one of the two mouse Gad gen es by gene targeting and also find defects in the formation of the pal ate. The striking similarity in phenotype between the receptor and lig and mutations clearly demonstrates a role for GABA signaling in normal palate development.