First Author | Harris RA | Year | 2011 |
Journal | Neurosci Lett | Volume | 488 |
Issue | 1 | Pages | 31-5 |
PubMed ID | 21056629 | Mgi Jnum | J:168344 |
Mgi Id | MGI:4888069 | Doi | 10.1016/j.neulet.2010.10.075 |
Citation | Harris RA, et al. (2011) Testing the silence of mutations: Transcriptomic and behavioral studies of GABA(A) receptor alpha1 and alpha2 subunit knock-in mice. Neurosci Lett 488(1):31-5 |
abstractText | Knock-in mice were constructed with mutations in the alpha1 (H(270), A(277)) and alpha2 (H(270), A(277)) subunits of the GABAA receptor, which resulted in receptors that lacked modulation by ethanol but retained normal responses to GABA in vitro. A key question is whether these mutant receptors also function normally in vivo. Perturbation of brain function was evaluated by gene expression profiling in the cerebral cortex and by behavioral pharmacology experiments with GABAergic drugs. Analysis of individual transcripts found only six transcripts that were changed in alpha1 knock-in mice and three in the alpha2 mutants (p<0.05, corrected for multiple comparisons). Two transcripts that are sensitive to neuronal activity, Arc and Fos, increased about 250% in the alpha2 mutants, and about 50% in the alpha1 mutants. Behavioral effects (loss of righting reflex, rotarod) of flurazepam and pentobarbital were not different between alpha2 mutants and wild-type, but they were enhanced for alpha1 knock-in mice. These results indicate that introduction of these mutations in the alpha2 subunit of the GABAA receptor does not produce marked perturbation of brain function, as measured by gene expression and GABAergic behavioral responses, but the same mutations in the alpha1 subunit produce more pronounced changes, especially in GABAergic function. |