International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 160 - MICROARRAY ANALYSIS OF TRANSCRIPTIONAL DIFFERENCES BETWEEN WILD TYPE AND MUTANT CNS IN THE CALCIUM CHANNEL MUTANT, DUCKY

TJ Wilkinson
University College London

2) Pritchard C, 2) Underhill P, 2) Tymowska-Lalanne Z, 1) Dolphin A, 1) Rees M
1) University College London, 2) MRC Harwell

The mouse mutant ducky (du), a model for absence epilepsy, is characterised by spike-wave seizures and ataxia. Mutations in the Cacna2d2 gene were found to underlie the phenotype in the original du strain and its allele, du2J. Cacna2d2 encodes the a2d2 voltage-dependent calcium channel subunit. The a2 and d chains are derived from proteolytic cleavage of the gene product, the d subunit acting as a membrane anchor for the extracellular a2 subunit. Both mutations are predicted to result in the loss of the full length protein and hence the d subunit.Cacna2d2 mRNA is strongly expressed in cerebellar Purkinje (P) cells, and du/du mice have abnormalities in their P cell dendritic tree. In addition, co-expression of the truncated protein with the Cav2.1/4 channel combination in vitro leads to a reduction in current density.To aid elucidation of the function of a2d2 we have performed microarray analysis at three different stages of development in du2J/du2J mice: embryonic, post-natal and adult. We expect that those transcripts identified as up- or down-regulated in the mutant mice will act up- or downstream of a2d2, either via the calcium channel as a whole, or directly though the subunit. We have identified a number of candidate transcripts, including a putative homeobox transcription factor and possible signalling molecules. Confirmation of these differences in expression between wild type and du2J CNS using QPCR is underway, and will be presented, along with more detailed analyses.


Abstracts * Officers * Bylaws * Application Form * Meeting Calendar * Contact Information * Home * Resources * News and Views * Membership

Base url http://imgs.org
Last modified: Saturday, November 3, 2012