JAX Mouse Strain Datasheet - 000291

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

Stock No:: 000291

Congenic

Cryo Recovery

Overview

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 adva...

Genetic overview

Genetic Background	Generation

Hm

Allele Type	Gene Symbol	Gene Name
Spontaneous	Hm	hammer toe

Kitl^Sl

Allele Type	Gene Symbol	Gene Name
Spontaneous	Kitl	kit ligand

Krt71^Ca-J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Krt71	keratin 71

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

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Research Applications

Developmental Biology Research
Cancer Research
Dermatology Research
Endocrine Deficiency Research
Immunology, Inflammation and Autoimmunity Research
Neurobiology Research
Reproductive Biology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

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.

Control Suggestions

Wild-type from the colony
000658 C3HeB/FeJ

Additional Information

Considerations for Choosing Controls

Genetics

Hm

Allele Symbol: Hm

Allele Name	hammertoe
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Hm, hammer toe
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	5

Kitl^Sl

Allele Symbol: Kitl^Sl

Allele Name	steel
Allele Type	Spontaneous
Allele Synonym(s)	Mgf^Sl; Sl
Gene Symbol and Name	Kitl, kit ligand
Gene Synonym(s)	Clo; Con; DCUA; DFNA69; FPH2; FPHH; Gb; Gb; KL-1; Kitlg; MGF; Mgf; Mgf; SCF; SF; SHEP7; SLF; Sl; Sl; Steel; Steel factor; blaze; blz; blz; cloud gray; contrasted; grizzle-belly; grizzle-belly; mast cell growth factor; steel; stem cell factor
Strain of Origin	C3H
Chromosome	10
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.

Krt71^Ca-J

Allele Symbol: Krt71^Ca-J

Allele Name	caracul Jackson
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Krt71, keratin 71
Gene Synonym(s)	AA589543; Ca; Ca; Cal4; Cal4; Cu; Cu; HYPT13; K6IRS1; KRT6IRS; KRT6IRS1; Krt2-6g; Krt2-6g; caracul; caracul-like 4; curly; expressed sequence AA589543; keratin complex 2, basic, gene 6g; mK6irs; mK6irs1
Strain of Origin	C57BL/6J
Chromosome	15
Molecular Note	Sequence analysis identified the spontaneous deletion of codon 140, comprised of nucleotides 418, 419, and 420 (CAA). The deleted codon predicted an asparagine in the alpha-helical rod domain. This molecular lesion is the same that has been identified in Krt2-6g^Ca-Rin, Ca^9J, and Ca^10J.

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)	AGSW; AGTI; AGTIL; ASP; As; As; SHEP9; agouti; agouti signal protein; agouti suppressor
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
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. 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.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Hm related

Developmental Biology Research
- Skeletal Defects

Genotype: Kitl^Sl related

Cancer Research
- Growth Factors/Receptors/Cytokines
- Increased Tumor Incidence
  - Gonadal Tumors
  - Gonadal Tumors: ovarian and testicular
Dermatology Research
- Color and White Spotting Defects
Developmental Biology Research
- Neural Crest Defects
Endocrine Deficiency Research
- Bone/Bone Marrow Defects
- Gonad Defects
- Hypothalamus/Pituitary Defects
- Skin Defects
Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
- Immunodeficiency
  - Mast Cell Deficiency
Neurobiology Research
- Hearing Defects
Reproductive Biology Research
- Developmental Defects Affecting Gonads
  - germ cell deficient
- Fertility Defects
- Gonadal Tumors
  - ovarian and testicular
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Mast Cell Deficiency
Sensorineural Research
- Hearing Defects

Genotype: Krt71^Ca-J related

Dermatology Research
- Color and White Spotting Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Krt71^Ca-J/Krt71⁺
C57BL/6J-Krt71^Ca-J

integument phenotype

abnormal coat appearance

curly vibrissae
- can be seen in mutant mice as early as one day of age
- whiskers are curved and grow irregularly

waved hair
- seen as early as 2 weeks of age util the second hair cycle around 4 weeks of age after which the coat loses its waviness but still has a subtle abnormal appearance.

Genotype: Krt71^Ca-J/Krt71^Ca-J
C57BL/6J-Krt71^Ca-J

integument phenotype

abnormal coat appearance
- homozygous and heterozygous mice are often indistinguishable

curly vibrissae
- can be seen in mutant mice as early as one day of age
- whiskers are curved and grow irregularly

waved hair
- seen as early as 2 weeks of age util the second hair cycle around 4 weeks of age after which the coat loses its waviness but still has a subtle abnormal appearance.

Genotype: Hm/Hm
C3Fe.Cg-Hm

limbs/digits/tail phenotype

abnormal phalanx morphology
- detectable by E14.5

interdigital webbing
- complete webbing with normal tibia
- webbing between digits 2,3,4, and 5 extends to the nails in the hindfeet; to the base of the distal phalanx in the forefeet
- webbing is extensive and prevents toe elongation, resulting in severe flexion at birth

skeleton phenotype

abnormal phalanx morphology
- detectable by E14.5

Genotype: Hm/Hm⁺
C3Fe.Cg-Hm

limbs/digits/tail phenotype

abnormal phalanx morphology
- detectable by E15
- on all four feet, the second phalanx of digits 2,3,4,and 5 is strongly flexed

interdigital webbing
- partial webbing
- webbing prevents toe elongation, resulting in flexion at birth

skeleton phenotype

abnormal phalanx morphology
- detectable by E15
- on all four feet, the second phalanx of digits 2,3,4,and 5 is strongly flexed

Genotype: Kitl^Sl/Kitl⁺
either: (involves: C3H * WC) or (involves: C3H * C57BL/6 * DBA/2J * WC)

hematopoietic system phenotype

anemia
- mice are slightly anemic

decreased mast cell number
- heterozygotes have decreased mast cell numbers in dorsal skin compared to wild-type

immune system phenotype

decreased mast cell number
- heterozygotes have decreased mast cell numbers in dorsal skin compared to wild-type

Genotype: Kitl^Sl/Kitl⁺
involves: C3H

pigmentation phenotype

belly spot
- most mice have a white spot on the belly

decreased ear pigmentation
- mice have light ears

decreased foot pigmentation
- mice have light feet

diluted coat color
- affected mice have overall dilution of coat color, more extreme on the belly than back
- reduced coat color

head blaze
- very occasionally mice have a white blaze between their eyes

head spot
- most mice have a white spot on the belly

hematopoietic system phenotype

anemia
- mice display less severe anemia than homozygotes

decreased erythrocyte cell number
- at 7-13 days of age, red blood cell counts are 20-30% lower than wild-type

hearing/vestibular/ear phenotype

decreased ear pigmentation
- mice have light ears

reproductive system phenotype

reproductive system phenotype
- heterozygotes are viable and fertile

craniofacial phenotype

decreased ear pigmentation
- mice have light ears

integument phenotype

abnormal vibrissa morphology
- mice have light whiskers

belly spot
- most mice have a white spot on the belly

decreased ear pigmentation
- mice have light ears

decreased foot pigmentation
- mice have light feet

diluted coat color
- affected mice have overall dilution of coat color, more extreme on the belly than back
- reduced coat color

head blaze
- very occasionally mice have a white blaze between their eyes

head spot
- most mice have a white spot on the belly

pallor
- some pups after birth are pale compared to littermates

growth/size/body region phenotype

decreased ear pigmentation
- mice have light ears

Genotype: Kitl^Sl/Kitl⁺
involves: 129/Sv * C3H

endocrine/exocrine gland phenotype

increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%)

reproductive system phenotype

increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%)

neoplasm

increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%)

increased tumor incidence
- male mice develop ~2-fold more tumors than controls

Genotype: Kitl^Sl/Kitl^Sl
involves: C3H

mortality/aging

lethality throughout fetal growth and development, complete penetrance
- an occasional mutant survives until birth
- no presumed homozygotes are born; homozygotes begin to die at ~E15-15.5 from anemia

nervous system phenotype

abnormal brain development
- at E10.5-12.5, small number of embryos, presumably homozygous, have brain abnormalities, including a collapsed brain, pseudoencephaly or a narrowed brain region
- from E14.5-17.5, some embryos show abnormal brain development (3/330) as described in younger embryos

myelencephalic blebs
- one E17.5 embryo displayed a bleb near the midline in the cervical region

spina bifida
- 4/330 embryos aged E14.5-17.5 displayed spina bifida

hematopoietic system phenotype

anemia
- starting around E13.5 and peaking at E14.5, presumed homozygotes display anemia recognized by overall paleness of the embryos

cardiovascular system phenotype

abnormal blood circulation
- in affected (anemic) animals, individual clumps or red blood cells can be seen in umbilical vessels; in controls, vessels are uniformly red with normal blood flow

reproductive system phenotype

infertility
- mice carrying two mutant alleles are sterile

pigmentation phenotype

absent skin pigmentation
- transplantation of skin grafts from E14, E15 and newborn mutants to normal siblings produced unpigmented hair

embryo phenotype

spina bifida
- 4/330 embryos aged E14.5-17.5 displayed spina bifida

integument phenotype

absent skin pigmentation
- transplantation of skin grafts from E14, E15 and newborn mutants to normal siblings produced unpigmented hair

pallor
- characteristic of anemic embryos

References

Additional References

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Huang E; Nocka K; Beier DR; Chu TY; Buck J; Lahm HW; Wellner D; Leder P; Besmer P. 1990. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 63(1):225-33. PubMed: 1698557 MGI: J:10751
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Additional - a related

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Additional - Kitl^Sl related

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Tokuda M; Kadokawa Y; Kurahashi H; Marunouchi T. 2007. CDH1 is a specific marker for undifferentiated spermatogonia in mouse testes. Biol Reprod 76(1):130-41. PubMed: 17035642 MGI: J:117360
Turner RT; Wong CP; Iwaniec UT. 2011. Effect of reduced c-Kit signaling on bone marrow adiposity. Anat Rec (Hoboken) 294(7):1126-34. PubMed: 21634019 MGI: J:175574
Turnquist HR; Zhao Z; Rosborough BR; Liu Q; Castellaneta A; Isse K; Wang Z; Lang M; Stolz DB; Zheng XX; Demetris AJ; Liew FY; Wood KJ; Thomson AW. 2011. IL-33 expands suppressive CD11b+ Gr-1 int and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol 187(9):4598-610. PubMed: 21949025 MGI: J:179437
Wang CH; Anderson N; Li SH; Szmitko PE; Cherng WJ; Fedak PW; Fazel S; Li RK; Yau TM; Weisel RD; Stanford WL; Verma S. 2006. Stem cell factor deficiency is vasculoprotective: unraveling a new therapeutic potential of imatinib mesylate. Circ Res 99(6):617-25. PubMed: 16931795 MGI: J:125065
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Additional - Krt71^Ca-J related

Dickie MM. 1966. Origin of Krt71<Ca-J> on C57BL/6J Mouse News Lett 34:30-31. MGI: J:161346
Kikkawa Y; Oyama A; Ishii R; Miura I; Amano T; Ishii Y; Yoshikawa Y; Masuya H; Wakana S; Shiroishi T; Taya C; Yonekawa H. 2003. A small deletion hotspot in the type II keratin gene mK6irs1/Krt2-6g on mouse chromosome 15, a candidate for causing the wavy hair of the caracul (Ca) mutation. Genetics 165(2):721-33. PubMed: 14573483 MGI: J:86407
Sundberg JP (ed.). 1994. Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. In: Handbook of Mouse Mutations with Skin and Hair Abnormalities: Animal Models and Biomedical Tools. CRC Press, Boca Raton. MGI: J:30359

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Hm

Allele Symbol: Hm

KitlSl

Allele Symbol: KitlSl

Krt71Ca-J

Allele Symbol: Krt71Ca-J

a

Allele Symbol: a

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Genotype: Hm related

Genotype: KitlSl related

Genotype: Krt71Ca-J related

Mammalian Phenotype Terms by Genotype

Genotype: Krt71Ca-J/Krt71+C57BL/6J-Krt71Ca-J

integument phenotype

Genotype: Krt71Ca-J/Krt71Ca-JC57BL/6J-Krt71Ca-J

integument phenotype

Genotype: Hm/HmC3Fe.Cg-Hm

limbs/digits/tail phenotype

skeleton phenotype

Genotype: Hm/Hm+C3Fe.Cg-Hm

limbs/digits/tail phenotype

skeleton phenotype

Genotype: KitlSl/Kitl+either: (involves: C3H * WC) or (involves: C3H * C57BL/6 * DBA/2J * WC)

hematopoietic system phenotype

immune system phenotype

Genotype: KitlSl/Kitl+involves: C3H

pigmentation phenotype

hematopoietic system phenotype

hearing/vestibular/ear phenotype

reproductive system phenotype

craniofacial phenotype

integument phenotype

growth/size/body region phenotype

Genotype: KitlSl/Kitl+involves: 129/Sv * C3H

endocrine/exocrine gland phenotype

reproductive system phenotype

neoplasm

Genotype: KitlSl/KitlSlinvolves: C3H

mortality/aging

nervous system phenotype

hematopoietic system phenotype

cardiovascular system phenotype

reproductive system phenotype

pigmentation phenotype

embryo phenotype

integument phenotype

References

Additional References

Additional - a related

Additional - Hm related

Additional - KitlSl related

Additional - Krt71Ca-J related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Kitl^Sl

Allele Symbol: Kitl^Sl

Krt71^Ca-J

Allele Symbol: Krt71^Ca-J

Genotype: Kitl^Sl related

Genotype: Krt71^Ca-J related

Genotype: Krt71^Ca-J/Krt71⁺
C57BL/6J-Krt71^Ca-J

Genotype: Krt71^Ca-J/Krt71^Ca-J
C57BL/6J-Krt71^Ca-J

Genotype: Hm/Hm
C3Fe.Cg-Hm

Genotype: Hm/Hm⁺
C3Fe.Cg-Hm

Genotype: Kitl^Sl/Kitl⁺
either: (involves: C3H * WC) or (involves: C3H * C57BL/6 * DBA/2J * WC)

Genotype: Kitl^Sl/Kitl⁺
involves: C3H

Genotype: Kitl^Sl/Kitl⁺
involves: 129/Sv * C3H

Genotype: Kitl^Sl/Kitl^Sl
involves: C3H

Additional - Kitl^Sl related

Additional - Krt71^Ca-J related