C3FeLe.Cg-a/a Hm Kitl^Sl Krt71^Ca-J/J

Stock number: 000291
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Detailed description

The multiple steel mutations (Kitl^Sl) behave in a semidominant fashion and cause deficiencies in pigment cells, germ cells, and blood cells paralleling those caused by the Kit locus mutations (dominant spotting alleles). Most of the alleles at steel locus cause severe anemia in utero and death by 15 to 16 days of gestation in homozygous mutant mice. However, compounds of two steel mutants (e.g. Kitl^Sl/Kitl^Sl-d) are viable, black-eyed white, are usually sterile in one or both sexes, and have severe macrocytic anemia. Heterozygous steel mice have a diluted coat color with a small amount of white spotting, are viable and fertile, and may have a slight macrocytic anemia. Primordial germ cells are absent in the nonviable steel homozygotes and severely reduced in steel heterozygotes. Mast cells are virtually absent in skin and other tissues of steel mutant mice. Tumors tend to develop in germ-cell-deficient ovaries with advancing age. This strain is also carrying the caracal-J (Krt71^Ca-J) and hammer toe (Hm) mutations.

Development

The linkage testing stock Hm, Sl, Ca^J was developed from various stocks. It started with a dancer (Dc/+) male mated to a steel (Sl/+) female in 1959. Dancer originated as a spontaneous mutation at the Jackson Laboratory in the C3H/He-Lep^ob stock at N4 in 1956. Steel (Kitl^Sl) arose spontaneously at the Jackson Laboratory in a C3H inbred strain and was maintained in a non-inbred multiple mutation stock by Dr. M.C. Green. A dancer steel (Dc/+ Kitl^Sl/+) mouse was crossed once to strain C57BL/6J. A dancer steel off spring was crossed to a homozygous caracul (Ca/Ca) mouse from an inbred caracul stock of Dr. G. D. Snell. Caracul was an early mutation that arose in a Swiss stock in the 1930s. The caracul steel cross was sibling mated for 4 generations without dancer and at F4 a caracul steel heterozygote was mated to a twirler (Tw/+) male. Twirler arose spontaneously in the PCS multiple recessive stock at Harwell and was imported to the Jackson Laboratory in 1961. The caracul steel twirler stock (Ca/+ Sl/+ Tw/+) was maintained by sibling and non-sibling matings until 1967 when twirler was replaced with hammer toe (Hm). Hammer toe arose spontaneously at the Jackson Laboratory in a linkage cross in which luxate (lu) was segregating. The three mutations Ca, Sl, and Hm were maintained together and backcrossed to C57BL/6J for 5 generations. In 1969 at N5 sib matings were used and in 1971 caracul (Ca) was replaced with caracul Jackson (Ca^J) which had arisen spontaneously in strain C57BL/6J. After several sibling matings with the 3 mutations segregating the Hm/+ Sl/+ Ca^J/+ stock was backcrossed to C57BL/6J to N19. In 1977 a B6.Cg-Hm/+ Sl/+ Ca^J/+ mouse at N19 was outcrossed to strain C3FeLe.B6-a/J and the strain was then maintained via continued backcrossing to strain C3FeLe.B6-a/J. It reached N76 in 1995. Embryos were generated for cryopreservation in 1989 by mating Hm/+ Sl/+ Ca^J/+ mice to a C3FeLe.B6-a/J.

Allele

Symbol: Hm
Name: hammertoe
MGI accession ID: MGI:1861096
Generation method: Spontaneous
Attributes: Not Applicable
Synonyms: Is(5;14)
Marker symbol: Hm
Marker name: hammer toe
Chromosome: 5
Strain of origin: Not Specified
Molecular note: A spontaneous mutation inserted upstream of the Shh promoter a 150 kb fragment of noncoding DNA from chromosome 14 between Slitrk1 and Slitrk6 that contains no coding sequences or non-coding RNAs.

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

Allele

Symbol: Krt71^Ca-J
Name: caracul Jackson
MGI accession ID: MGI:1855992
Generation method: Spontaneous
Marker symbol: Krt71
Marker name: keratin 71
Marker synonyms: Ca; Cal4; Cu; HYPT13; K6IRS1; Krt2-6g; KRT6IRS; KRT6IRS1; mK6irs; mK6irs1
Chromosome: 15
Strain of origin: C57BL/6J
Molecular note: Sequence analysis identified the spontaneous deletion of asparagine codon 139 or 140, through the deletion of CAA / ACA / AAC from the AACAACAA sequence at codong nucleotides 415-422. The deleted codon is located in the alpha-helical rod domain. This molecular lesion is the same that has been identified in Krt71^Ca-Rin, Krt71^Ca-9J, and Krt71^Ca-10J.

Allele

Symbol: Kitl^Sl
Name: steel
MGI accession ID: MGI:1856161
Generation method: Spontaneous
Synonyms: Mgf^Sl; Sl
Marker symbol: Kitl
Marker name: kit ligand
Marker synonyms: blz; DCUA; DFNA69; FPH2; FPHH; Gb; grizzle-belly; Kitlg; KL-1; Mgf; SCF; SF; SHEP7; Sl; SLF; Steel; Steel factor; stem cell factor; WS2F
Chromosome: 10
Strain of origin: C3H
Molecular note: By Southern blotting, it was concluded that this allele contains a deletion encompassing most, if not all, of the coding region of the gene. A probe corresponding to nucleotides 6 to 685 of the cDNA failed to hybridize to DNA obtained from embryos homozygous for this allele. PCR analysis with primers for sequences at various distances from the Kit gene narrowed the 5' and 3' deletion endpoints to a 350 and a 380 base-pair region, respectively. Sequencing of the product of PCR using primers designed to span the deletion revealed that it extends through 973,366 base pairs on Chromosome 10 between nucleotide positions 99,177,807 and 100,151,173 (NCBI Map Viewer, Build 36.1), with a 4-base pair insertion joining the deletion endpoints, and contains 6 predicted and 3 known genes.