B6C3Fe a/a-Dst^dt-J/J

Stock number: 000211
Product name: dystonia musculorum Jackson
Research areas: Developmental Biology Research, Mouse/Human Gene Homologs, Neurobiology Research

Detailed description

Mice homozygous for the dystonia musculorum-J spontaneous mutation (Dst^dt-J)are recognizable at 7 to 10 days of age by clasping of the hindlimbs when mice are lifted by the tail. There is increasing incoordination with alternating hyperextension and hyperflexion of the limbs but no obvious paralysis. Many affected animals die before weaning, but some survive several months. The clinical condition becomes relatively stationary after the first phase of deterioration. Histologically, the nervous system shows degenerative changes and progressive loss of nerve fibers in the central and peripheral branches of the sensory ganglion cells of the spinal and cranial nerves, in the central sensory pathways, and in peripheral sensory structures such as skin, Pacinian corpuscles, and muscle spindles. In the PNS, there is some segmental demyelination and other abnormalities of the myelin sheaths.

Development

The dystonia Jackson (dt-J) mutation arose spontaneously in 1957 in the C3HeB/FeDi inbred strain when that strain was at F20. dt-J was initially named athetoid (ah) but was changed to dt-J in 1964 when D. S. Falconer in Edinburgh performed a positive allele test with the original dystonia (dt) mutation (Lane 1958; Falconer 1964). The dt-J allele was maintained heterozygote x heterozygote via test breeding then at F33 was changed to homozygous ovarian transplant backcrossed to C57BL/6J followed by intercross. This reached F33N4 in 1973. At F33N11 the strain was outcrossed once to C3HeB/FeJ A/A, intercrossed once and subsequently maintained by homozygous ovarian transplant crossed to B6C3Fe-a/a F1 then intercross. In 1979 this strain reached N6, in 1983 it reached N18, and in 2004 it reached N59.

Allele

Symbol: Dst^dt-J
Name: dystonia musculorum Jackson
MGI accession ID: MGI:1856021
Generation method: Spontaneous
Synonyms: ah; athetoid; dt
Marker symbol: Dst
Marker name: dystonin
Marker synonyms: 2310001O04Rik; A830042E19Rik; ah; athetoid; BP240; BPA; Bpag; Bpag1; BPAG1-n; bullous pemphigoid antigen 1; CATX15; CATX-15; D6S1101; DMH; DT; EBS3; EBSB2; HSAN6; Macf2; mKIAA0728; nmf203; nmf339
Chromosome: 1
Strain of origin: C3HeB
General note: At least 27 remutations have occurred at The Jackson Laboratory. The first, Dst^dt-J, occurred spontaneously in C3HeB, and was originally designated athetoid (J:24773). It was soon shown to be an allele of the dt mutation, however (J:160)

Allele

Symbol: a
Name: nonagouti
MGI accession ID: MGI:1855937
Generation method: Spontaneous
Marker symbol: a
Marker name: nonagouti
Marker synonyms: agouti; agouti signal protein; AGSW; AGTI; AGTIL; As; ASP; SHEP9
Chromosome: 2
Strain of origin: old mutant of the mouse fancy
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 a^t-2Gso and A^w-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.
General note: Insertion of the LV30 retrotransposon without the beta4 retrovirus sequence does not cause the nonagouti phenotype. J:278039