Cleft palate in mice with a targeted mutation in the γ-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67
Abstract
The functions of neurotransmitters in fetal development are poorly understood. Genetic observations have suggested a role for the inhibitory amino acid neurotransmitter γ-aminobutyric acid (GABA) in the normal development of the mouse palate. Mice homozygous for mutations in the β-3 GABAA receptor subunit develop a cleft secondary palate. GABA, the ligand for this receptor, is synthesized by the enzyme glutamic acid decarboxylase. We have disrupted one of the two mouse Gad genes by gene targeting and also find defects in the formation of the palate. The striking similarity in phenotype between the receptor and ligand mutations clearly demonstrates a role for GABA signaling in normal palate development.
Acknowledgments
We thank C. Lenz, M. Allen, G. Peterson, E. Nakashima, M. Wagstaff, and S. Barnett for excellent technical assistance and L. Oswald for preparation of the manuscript.
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Copyright © 1997, The National Academy of Sciences of the USA.
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Accepted: August 14, 1997
Published online: October 14, 1997
Published in issue: October 14, 1997
Acknowledgments
We thank C. Lenz, M. Allen, G. Peterson, E. Nakashima, M. Wagstaff, and S. Barnett for excellent technical assistance and L. Oswald for preparation of the manuscript.
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Cleft palate in mice with a targeted mutation in the γ-aminobutyric acid-producing enzyme glutamic acid decarboxylase 67, Proc. Natl. Acad. Sci. U.S.A.
94 (21) 11451-11455,
https://doi.org/10.1073/pnas.94.21.11451
(1997).
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