| First Author | Thompson CL | Year | 1998 |
| Journal | Brain Res Mol Brain Res | Volume | 60 |
| Issue | 2 | Pages | 282-90 |
| PubMed ID | 9757064 | Mgi Jnum | J:50701 |
| Mgi Id | MGI:1309599 | Doi | 10.1016/s0169-328x(98)00205-8 |
| Citation | Thompson CL, et al. (1998) Decreased expression of GABAA receptor alpha6 and beta3 subunits in stargazer mutant mice: a possible role for brain-derived neurotrophic factor in the regulation of cerebellar GABAA receptor expression?. Brain Res Mol Brain Res 60(2):282-90 |
| abstractText | The cerebellar granule cells of the spontaneous recessive mutant mouse strain, stargazer (stg/stg), fail to express brain-derived neurotrophic factor mRNA. This deficit is exclusive to these neurons and is believed to underlie the motor irregularities displayed by stg/stg, though the molecular basis for their phenotype has still to be resolved. Brain-derived neurotrophic factor has been shown to play a role in the postnatal maturation of cerebellar granule cells. Differentiation of these neurons, postnatally, is characterised by a switch in their GABA(A) receptor subunit expression profile. Notably, the GABA(A) receptor alpha 6 subunit, which is specific to these neurons, becomes detectable at postnatal days 10-14 (P10- 14). To determine whether cerebellar GABA(A) receptor expression has been compromised in stg/stg mice, the expression levels of GABA(A) receptor alpha 1, alpha 6, beta 2 and beta 3 subunits were compared between stg/stg mice and the appropriate wild-type background strain, C57BL/6J (+ / +). By quantitative immunoblotting, it was found that the expression of the alpha 6 and beta 3 subunits was 23 +/- 8% and 38 +/- 12% (mean +/- S.E.M., n = 6) of control (+ / +) levels, respectively. In contrast, the expression of the alpha 1 and beta 2 subunits was not significantly different from controls, being 116 +/- 11% and 87 +/- 24% (mean +/- S.E.M., n = 6) of +/+ levels, respectively. Total specific [H-3]Ro15-4513 binding activity detected in cerebellar membranes prepared from stg/stg was not significantly different from +/+ mice. However, the benzodiazepine agonist-insensitive subtype of [H-3]Ro15-4513 binding activity, a pharmacological motif of alpha 6 subunit-containing GABA(A) receptors, was lower in stg/stg mice relative to the +/+ strain which correlated with the lowered level of alpha 6 subunit expression. Thus, we have identified an abnormality in the GABA(A) receptor profile of stg/stg mutant mice that might underpin its irregular phenotype. (C) 1998 Elsevier Science B.V. All rights reserved. |
