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

a

Allele Type	Gene Symbol	Gene Name
Spontaneous	a	nonagouti

Krt71^Ca-J

Allele Type	Gene Symbol	Gene Name
Spontaneous	Krt71	keratin 71

Kitl^Sl

Allele Type	Gene Symbol	Gene Name
Spontaneous	Kitl	kit ligand

Hm

Allele Type	Gene Symbol	Gene Name
Spontaneous (Not Applicable)	Hm	hammer toe

View Genetics

Research Applications

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

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

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.

Control Suggestions

Wild-type from the colony
000658 C3HeB/FeJ

Additional Information

Considerations for Choosing Controls

Genetics

a

Allele Symbol: a

Allele Name	nonagouti
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	a, nonagouti
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	2
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 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.

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)
Strain of Origin	C57BL/6J
Chromosome	15
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.

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)
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.

Hm

Allele Symbol: Hm

Allele Name	hammertoe
Allele Type	Spontaneous (Not Applicable)
Allele Synonym(s)	Is(5;14)
Gene Symbol and Name	Hm, hammer toe
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	5
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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: ovarian and testicular
  - Gonadal Tumors
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
Reproductive Biology Research
- Fertility Defects
- Gonadal Tumors
  - ovarian and testicular
- Developmental Defects Affecting Gonads
  - germ cell deficient
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Mast Cell Deficiency
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Mast Cell Deficiency
- Growth Factors/Receptors/Cytokines
Neurobiology Research
- Hearing Defects
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: Kitl^Sl/Kitl^Sl
involves: C3H

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

pigmentation phenotype

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

reproductive system phenotype

infertility
- mice carrying two mutant alleles are sterile

embryo phenotype

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

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

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

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

Genotype: Kitl^Sl/Kitl⁺
involves: C3H

craniofacial phenotype

decreased ear pigmentation
- mice have light ears

integument phenotype

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

pallor
- some pups after birth are pale compared to littermates

decreased ear pigmentation
- mice have light ears

abnormal vibrissa morphology
- mice have light whiskers

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

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

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

decreased foot pigmentation
- mice have light feet

mammalian phenotype

reproductive system phenotype
- Normal - heterozygotes are viable and fertile

pigmentation phenotype

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

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

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

decreased foot pigmentation
- mice have light feet

decreased ear pigmentation
- mice have light ears

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

growth/size/body region phenotype

decreased ear pigmentation
- mice have light ears

hearing/vestibular/ear phenotype

decreased ear pigmentation
- mice have light ears

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

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

integument phenotype

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

abnormal coat appearance

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: 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: Hm/Hm
C3Fe.Cg-Hm

limbs/digits/tail phenotype

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

abnormal phalanx morphology
- detectable by E14.5

skeleton phenotype

abnormal phalanx morphology
- detectable by E14.5

Genotype: Hm/Hm⁺
C3Fe.Cg-Hm

limbs/digits/tail phenotype

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

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

skeleton phenotype

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

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

neoplasm

increased testicular teratoma incidence
- 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%)
- incidence is 6.92% compared to ~2.6% in controls

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

reproductive system phenotype

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

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

integument phenotype

abnormal coat appearance
- homozygous and heterozygous mice are often indistinguishable

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.

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

References

Additional References

Arguello F; Furlanetto RW; Baggs RB; Graves BT; Harwell SE; Cohen HJ; Frantz CN. 1992. Incidence and distribution of experimental metastases in mutant mice with defective organ microenvironments (genotypes Sl/Sld and W/Wv). Cancer Res 52(8):2304-9PubMed: 1559233 MGI: J:468
Hayashi C; Sonoda T; Nakano T; Nakayama H; Kitamura Y. 1985. Mast-cell precursors in the skin of mouse embryos and their deficiency in embryos of Sl/Sld genotype. Dev Biol 109(1):234-41PubMed: 3987963 MGI: J:7810
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):225-33PubMed: 1698557 MGI: J:10751
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):721-33PubMed: 14573483 MGI: J:86407
Kimura S; Terashima T; Schaumann BA; Shimada M; Shiota K. 2000. Pads and flexion creases on the plantar surface of hammertoe mutant mouse (Hm) Anat Rec 260(1):26-32PubMed: 10967533 MGI: J:64344
Murphy ED. 1977. Effects of mutant steel alleles on leukemogenesis and life-span in the mouse. J Natl Cancer Inst 58(1):107-10PubMed: 319242 MGI: J:5758
Schrott A; Egg G; Spoendlin H. 1988. Intermediate filaments in the cochleas of normal and mutant (w/wv, sl/sld) mice. Arch Otorhinolaryngol 245(4):250-4PubMed: 2460075 MGI: J:9423
Schrott A; Spoendlin H. 1987. Pigment anomaly-associated inner ear deafness. Acta Otolaryngol (Stockh) 103(5-6):451-7PubMed: 3618172 MGI: J:8813
Wolf NS. 1978. Dissecting the hematopoietic microenvironment. II. The kinetics of the erythron of the S1/S1d mouse and the dual nature of its anemia. Cell Tissue Kinet 11(4):325-34PubMed: 688326 MGI: J:6031
Zsebo KM; Williams DA; Geissler EN; Broudy VC; Martin FH; Atkins HL; Hsu RY; Birkett NC; Okino KH; Murdock DC; Jacobsen FW; Langley KE; Smith KA; Takeishi T; Cattanach BM; Galli SJ; Suggs SV. 1990. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63(1):213-24PubMed: 1698556 MGI: J:10750

Additional - a related

Additional - Hm related

Additional - Kitl^Sl related

Additional - Krt71^Ca-J related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Breeding Considerations

Krt71^Ca-J, Kitl^Sl and Hm are not linked and thus mice with various combinations of these mutations will be found from an Heterozygote x F1 breeding scheme.
- Additional Breeding and Husbandry Support
Citation
When using the C3FeLe.Cg-a/a Hm Kitl^Sl Krt71^Ca-J/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000291 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Krt71<Ca-J>, Heterozygous or Wild-type for Kitl<Sl>, Heterozygous or Wild-type for Hm

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

a

Allele Symbol: a

Krt71Ca-J

Allele Symbol: Krt71Ca-J

KitlSl

Allele Symbol: KitlSl

Hm

Allele Symbol: Hm

Disease Terms

Research Areas By Phenotype

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: KitlSl/KitlSlinvolves: C3H

cardiovascular system phenotype

pigmentation phenotype

reproductive system phenotype

embryo phenotype

hematopoietic system phenotype

integument phenotype

mortality/aging

nervous system phenotype

Genotype: KitlSl/Kitl+involves: C3H

craniofacial phenotype

integument phenotype

mammalian phenotype

pigmentation phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

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

integument phenotype

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

hematopoietic system phenotype

immune system 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+involves: 129/Sv * C3H

endocrine/exocrine gland phenotype

neoplasm

reproductive system phenotype

Genotype: Krt71Ca-J/Krt71Ca-JC57BL/6J-Krt71

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

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Krt71^Ca-J

Allele Symbol: Krt71^Ca-J

Kitl^Sl

Allele Symbol: Kitl^Sl

Genotype: Kitl^Sl related

Genotype: Krt71^Ca-J related

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

Genotype: Kitl^Sl/Kitl⁺
involves: C3H

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

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

Genotype: Hm/Hm
C3Fe.Cg-Hm

Genotype: Hm/Hm⁺
C3Fe.Cg-Hm

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

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

Additional - Kitl^Sl related

Additional - Krt71^Ca-J related