GABAA/benzodiazepine receptor alpha 6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei: expression in developing and mutant mice.

The gamma aminobutyric acidA/benzodiazepine (GABAA/BZ) receptor is a multisubunit (alpha, beta, gamma, delta, and rho) ligand-gated chloride channel; there are several variants of the alpha, beta, and gamma subunits, each of which has been localized throughout the central nervous system. A large number of GABAA/BZ subunit variants are expressed within the cerebellar cortex. In previous studies from other laboratories, alpha 6 subunit mRNA has been reported to be present exclusively in cerebellar granule cells. The developmental expression of alpha 6 mRNA in cerebellar and cochlear granule cells is of interest because it has been suggested that each of these cell types is derived from a common precursor pool. The polymerase chain reaction was used to generate a cDNA fragment encoding a portion of the M3-M4 intracellular loop of the alpha 6 subunit of the GABAA/BZ receptor. A [35S] riboprobe, transcribed from this cDNA fragment, was used to examine the expression of the alpha 6 subunit mRNA by in situ hybridization in developing normal mice and in adult mutant mice with known deficits in synaptic circuitry. A strong hybridization signal was observed over the granule cell layers of both the cerebellum and cochlear nuclei in adult mice. The signal over the cochlear nuclei appeared after birth toward the end of postnatal week 1, coinciding with the appearance of labeling in the cerebellar cortex. The intensity of the hybridization signal in both regions increased rapidly until postnatal day 14, after which it increased more gradually, reaching adult levels during postnatal week 3.(ABSTRACT TRUNCATED AT 250 WORDS)