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

Nature volume 364, pages 448–450 (1993)Cite this article

Abstract

THE mouse pink-eyed cleft-palate (pcp ) mutation is characterized by hypopigmentation associated with cleft palate, neurological disorders and runting1,2. Most pcp homozygotes are born with cleft palate and die shortly after birth, presumably as a result of feeding problems3. A few exceptional pcp mutants live beyond this stage but display tremor and jerky gait2. We report here that the genes encoding the γ-aminobutyric acid type A (GABAA) receptor sub-units α5 (originally described as α4; ref. 4), β3 and γ3 are disrupted by a deletion in pcp mice. We also show that the α5 and γ3 genes are located between the p and β3 genes on mouse chromosome 7. The pcp deletion leads to alterations of binding properties of the GABAA receptors in the brain, providing an in vivo model system for studying GABAA receptor function. The human homologue of the region deleted in pcp mice is associated with Angelman syndrome5–9. Thus, pcp mice may be useful in defining the region containing the gene(s) for this syndrome.

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Author notes

  1. Murray H. Brilliant: To whom correspondence should be addressed.

Authors and Affiliations

  1. The Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania, 19111, USA

    Yoshimichi Nakatsu, Donna Durham-Pierre, John M. Gardner, Heather J. McDanel & Murray H. Brilliant

  2. Department of Pharmacology, School of Medicine, University of California, Los Angeles, California, 90024, USA

    Rachel F. Tyndale, Timothy M. DeLorey, Q. Nguyen & Richard W. Olsent

  3. Department of Biology, University of California, Los Angeles, California, 90024, USA

    Rachel F. Tyndale & Allan J. Tobin

  4. Genetics Division, Children's Hospital, Boston, Massachusetts, 02115, USA

    Joseph Wagstaff & Marc Lalando

  5. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Joseph Wagstaff & Marc Lalando

  6. Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA

    Marc Lalando

  7. Department of Pharmacology, University of Colorado Health Science Center, Denver, Colorado, 80262, USA

    James M. Sikela

Authors
  1. Yoshimichi Nakatsu
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  2. Rachel F. Tyndale
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  4. Donna Durham-Pierre
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  7. Q. Nguyen
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  8. Joseph Wagstaff
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  9. Marc Lalando
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  13. Murray H. Brilliant
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Nakatsu, Y., Tyndale, R., DeLorey, T. et al. A cluster of three GABAA receptor subunit genes is deleted in a neurological mutant of the mouse p locus. Nature 364, 448–450 (1993). https://doi.org/10.1038/364448a0

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