Clustering of GABA_A receptor alpha1, alpha6, beta2, and gamma2 subunit
genes on mouse chromosome 11/human chromosome 5 may have functional
significance for coordinating expression patterns, but until now there
has been no evidence for cross-talk between the genes. However, altering
the structure of the alpha6 gene, specifically expressed in the
cerebellum, with neomycin gene insertions in two different experiments
unexpectedly reduced the expression of the widespread alpha1 and beta2
genes in the forebrain. There were corresponding reductions in the
levels of alpha1 and beta2 subunit proteins and in autoradiographic
ligand binding densities to GABA_A receptors in the forebrain of
alpha6-/- mice. The gamma2 mRNA level was not changed, nor were beta3
and delta mRNAs. The data suggest that elements in the neo gene may have
an influence over long distances in the GABA_A subunit gene complex on
as yet undefined structures coordinating the expression of the alpha1
and beta2 genes.