Concordance between isolated cleft palate in mice and alterations within a region including the gene encoding the β3 subunit of the type a γ-aminobutyric acid receptor

Cymbeline T. Culiat, Lisa Stubbs, Robert D. Nicholls, Clyde S. Montgomery, Liane B. Russell, Dabney K. Johnson, Eugene M. Rinchik

Research output: Contribution to journalArticlepeer-review

Abstract

Genetic and molecular analyses of a number of radiation-induced deletion mutations of the pink-eyed dilution (p) locus in mouse chromosome 7 have identified a specific interval on the genetic map associated with a neonatally lethal mutation that results in cleft palate. This interval, closely linked and distal to p, and bracketed by the genes encoding the α5 and β3 subunits of the type A γ-aminobutyric acid receptor (Gabra5 and Gabrb3, respectively), contains a gene(s) (cp1; cleft palate 1) necessary for normal palate development. The cp1 interval extends from the distal breakpoint of the prenatally lethal p83FBF0 deletion to the Gabrb3 locus. Among 20 p deletions tested, there was complete concordance between alterations at the Gabrb3 transcription unit and inability to complement the cleft-palate defect. These mapping data, along with previously described in vivo and in vitro teratological effects of γ-aminobutyric acid or its agonists on palate development, suggest the possibility that a particular type A γ-aminobutyric acid receptor that includes the β3 subunit may be necessary for normal palate development. The placement of the cp1 gene within a defined segment of the larger D15S12h (p)-D15S9h-1 interval in the mouse suggests that the highly homologous region of the human genome, 15q11-q13, be evaluated for a role(s) in human fetal facial development.

Original languageEnglish (US)
Pages (from-to)5105-5109
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number11
DOIs
StatePublished - Jun 1 1993
Externally publishedYes

Keywords

  • Complementation analysis
  • Complex syndromes
  • Deletion mapping
  • Facial development
  • p-locus mutations

ASJC Scopus subject areas

  • General

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