Details

Autor(en) / Beteiligte

• Coleman, Michael P.
• Conforti, Laura
• Buckmaster, E. Anne
• Tarlton, Andrea
• Ewing, Robert M.
• Brown, Michael C.
• Lyon, Mary F.
• Perry, V. Hugh

Titel

An 85-kb Tandem Triplication in the Slow Wallerian Degeneration (Wlds) Mouse

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1998-08, Vol.95 (17), p.9985-9990

Ort / Verlag

United States: National Academy of Sciences of the United States of America

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL/Wlds) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL/Wldsamong 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences (``illegitimate'' or ``nonhomologous'' recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wldsmice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.