Comparative transcription map of the wobbler critical region on mouse chromosome 11 and the homologous region on human chromosome 2p13-14

Abstract

Background: To support the positional cloning of the mouse mutation wobbler (wr) the corresponding regions on human Chr2p13-14 and mouse Chr11 were analyzed in detail and compared with respect to gene content, order, and orientation. Results: The gene content of the investigated regions was highly conserved between the two species: 20 orthologous genes were identified on our BAC/YAC contig comprising 4.5 Mb between REL/Rel and RAB1A/Rab1a. Exceptions were pseudogenes ELP and PX19 whose mouse counterparts were not located within the analyzed region. Two independently isolated genomic clones indicate an inversion between man and mouse with the inverted segment being identical to the wobbler critical interval. We investigated the wobbler critical region by extensive STS/EST mapping and genomic sequencing. Additionally, the full-length cDNA sequences of four newly mapped genes as well as the previously mapped gene Otx1 were established and subjected to mutation analysis. Our data indicate that all genes in the wr critical region have been identified. Conclusion: Unexpectedly, neither mutation analysis of cDNAs nor levels of mRNAs indicated which of the candidate genes might be affected by the wr mutation. The possibility arises that there might be hitherto unknown effects of mutations, in addition to structural changes of the mRNA or regulatory abnormalities.

Brainstem motor nuclei respond differentially to degenerative disease in the mutant mouse wobbler

“…Increasingly from 3 weeks of age, wobbler mice can be identified by their smaller size, a low frequency tremor that causes the head to wobble and weakness of the forelimbs. They are homozygote for an unidentified recessive mutant gene that maps to an identified region of chromosome 11 [22]. All animals were killed by transcardiac perfusion with buffered 4% paraformaldehyde solution (50 ml) following a brief perfusion with saline whilst under deep sodium pentobarbitone‐induced anaesthesia, according to procedures approved by the local Ethical Review Committee and licensed by the UK government Home Office.…”

Role of GARP Vesicle Tethering Complex in Golgi Physiology

“…The chromosomal mapping of the wobbler locus revealed that the disease-causing gene was autosomal, recessive, and presumably unique. The wobbler gene was found in proximal mouse chromosome 11 [ 80 , 81 ], which is homologous to human chromosome 2p13-14 [ 82 ]. This mutation was identified using positional cloning as a point mutation in the final exon of the VPS54 gene.…”