Dominant megacolon (Sox10Dom), expressed as a variable size white belly spot and white feet arose, spontaneously in a hybrid stock carrying bouncy (B6C3Fe a/a-bc) at N12 in 1979. Already on a predominantly B6C3Fe-a/a F1 background it was continued on this hybrid background by mating a Sox10Dom/+ mouse to the F1 hybrid each generation. Sox10Dom was cryopreserved in 1986 by mating heterozygous females at N34F1 to B6C3Fe-a/a F1 hybrid males and discontinued on the shelf in 1988.
|Gene Symbol and Name||a, nonagouti|
|Strain of Origin||old mutant of the mouse fancy|
|General Note||Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039|
|Molecular Note||Characterization of this allele shows an insertion of DNA comprised of a 5.5kb virus-like element, VL30, into the first intron of the agouti gene. The VL30 element itself contains an additional 5.5 kb sequence, flanked by 526 bp of direct repeats (beta4 retroviral sequence). The host integration site is the same as for at-2Gso and Aw-38J and includes a duplication of four nucleotides of host DNA and a deletion of 2 bp from the end of each repeat. Northern analysis of mRNA from skin of homozygotes shows a smaller agouti message and levels 8 fold lower than found in wild-type.|
|Allele Name||dominant megacolon|
|Allele Type||Spontaneous (Dominant negative)|
|Gene Symbol and Name||Sox10, SRY (sex determining region Y)-box 10|
|Strain of Origin||C57BL/6JLe|
|General Note||Genbank ID for this mutation: AF047389 |
Protein produced is a truncation that acts as a dominant negative see J:160219
|Molecular Note||Duplication of a G residue (C in forward strand) in the GGGG sequence overlapping codons G193 and E194 results in a translational frame shift in the postulated CDS, changing glutamic acid codon 194 to a glycine codon and replacing the putative activation domain with 99 novel amino acids ahead of a premature translational termination signal. Northern analysis using a Sox10 cDNA probe detected reduced amounts of transcript in E12.5 and E16.5 homozygous mutant embryos, compared to wild-type embryos (J:45117). A c.32A>T transversion in the CDS is predicted to cause a substitution of glutamate with valine at postion 11 (p.E11V). Whole mount in situ hybridization studies of homozygous mutant E10.5 embryos did not detect Sox10 expression in cranial ganglia and nerves, detected reduced expression along motor nerves, and detected expression in the trunk neural crest-derived dorsal root ganglia. In situ hybridization studies did not detect expression in intestine of homozygous mutant E14.5 embryos. (J:47640). In situ hybridization studies of E11.5 homozygous mutant embryos detected reduced numbers of cells that express the mutant allele in dorsal root ganglia and along the spinal nerves (J:67383).|
Approximately 30% of Dom/+ heterozygotes die between 21-30 days of age.
When using the B6C3Fe a/a-Sox10Dom/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000290 in your Materials and Methods section.