International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 107 - POSITIONAL CLONING OF THE TEETERING GENE

AH White
University College London

Gardiner RM, Rees M
University College London

The recessive lethal teetering mutation arose spontaneously in C3H/HeJ mice in 1958. Teetering mice are ataxic and have recently been shown to display bilaterally synchronous spike and wave pattern on EEG (Noebels, personal communication). These symptoms are characteristic of other mouse models of absence epilepsy such as ducky. The teetering gene (tn) was originally mapped to the distal end of mouse Chromosome 11, in a region showing conserved synteny with human 17q25.3.  We aim to use an intersubspecific intercross to refine the location of tn and subsequently a positional candidate approach to identify the gene containing the causative mutation.Over 500 F2 teetering offspring (tn/tn) from a (B6C3Fe-a/a-tn x CAST/Ei) F1 intercross have been obtained and are being typed for a panel of microsatellite markers spanning the telomeric end of Chromosome 11.  The results of this screen narrowed the tn critical region to 1cM between D11Mit104 (79cM) and D11Mit69 (80cM).  In order to more finely map tn, novel polymorphic microsatellites and SNPs within the region have been identified and utilised as markers. This process has further localised tn to a region of approximately 1Mb between the genes for neuronal pentraxin (Nptx1) and phosphodiesterase 6G (Pde6g).  Analysis of the tn critical region using mouse draft genome assembly resources (http://genome.cse.ucsc.edu/ and http://www.ensembl.org/Mus_musculus/) shows no obvious candidates, such as ion channel genes.  Known genes, gene predictions and ESTs within the critical region are being evaluated as candidates using northern blotting, RT-PCR and DNA sequencing.


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