JAX
Mouse Strain Datasheet - 000124
B6.Cg-KitlSl Krt71Ca/J
The multiple steel mutations (KitlSl) 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. KitlSl/KitlSl-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...
Read More +Genetic overview
| Genetic Background | Generation |
|---|---|
|
000663 C57BL/6By |
|
KitlSl
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Spontaneous | Kitl | kit ligand |
Krt71Ca
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Spontaneous | Krt71 | keratin 71 |
Research Applications
- Cancer Research
- Dermatology Research
- Developmental Biology Research
- Endocrine Deficiency Research
- Immunology, Inflammation and Autoimmunity Research
- Neurobiology Research
- Reproductive Biology Research
- Research Tools
Detailed Description
The multiple steel mutations (KitlSl) 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. KitlSl/KitlSl-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.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described.We will modify the strain description if necessary as published results become available.
Control Suggestions
- Wild-type from the colony
- 001139 C57BL/6ByJ
Additional Information
KitlSl
Allele Symbol: KitlSl
| Allele Name | steel |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | MgfSl; 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. |
Krt71Ca
Allele Symbol: Krt71Ca
| Allele Name | caracul |
|---|---|
| Allele Type | Spontaneous |
| Allele Synonym(s) | Ca |
| 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 | Swiss stock |
| Chromosome | 15 |
| Molecular Note | Sequence analysis of Krt2-6g identified the transversion of an adenosine to a cytosine at nucleotide 1292, resulting in an alanine to aspartic acid missense mutation at codon 431 (A431D). |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
Genotype: KitlSl 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
- Developmental Defects Affecting Gonads
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- Mast Cell Deficiency
- Immunology, Inflammation and Autoimmunity Research
- Sensorineural Research
- Hearing Defects
Genotype: Krt71Ca related
- Dermatology Research
- Skin and Hair Texture 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: KitlSl/Kitl+
either: (involves: C3H * WC) or (involves: C3H * C57BL/6 * DBA/2J * WC)
hematopoietic system phenotype
- anemia
- mice are slightly anemic (MGI Ref ID J:6084)
- decreased mast cell number
- heterozygotes have decreased mast cell numbers in dorsal skin compared to wild-type (MGI Ref ID J:6084)
immune system phenotype
- decreased mast cell number
- heterozygotes have decreased mast cell numbers in dorsal skin compared to wild-type (MGI Ref ID J:6084)
Genotype: KitlSl/Kitl+
involves: C3H
pigmentation phenotype
- decreased ear pigmentation
- mice have light ears (MGI Ref ID J:3399)
- decreased foot pigmentation
- mice have light feet (MGI Ref ID J:3399)
- diluted coat color
- head blaze
- very occasionally mice have a white blaze between their eyes (MGI Ref ID J:3399)
- head spot
- most mice have a white spot on the belly (MGI Ref ID J:3399)
hematopoietic system phenotype
- anemia
- mice display less severe anemia than homozygotes (MGI Ref ID J:3399)
- decreased erythrocyte cell number
- at 7-13 days of age, red blood cell counts are 20-30% lower than wild-type (MGI Ref ID J:3399)
hearing/vestibular/ear phenotype
- decreased ear pigmentation
- mice have light ears (MGI Ref ID J:3399)
reproductive system phenotype
- reproductive system phenotype
- heterozygotes are viable and fertile (MGI Ref ID J:3399)
craniofacial phenotype
- decreased ear pigmentation
- mice have light ears (MGI Ref ID J:3399)
integument phenotype
- abnormal vibrissa morphology
- mice have light whiskers (MGI Ref ID J:3399)
- decreased ear pigmentation
- mice have light ears (MGI Ref ID J:3399)
- decreased foot pigmentation
- mice have light feet (MGI Ref ID J:3399)
- diluted coat color
- head blaze
- very occasionally mice have a white blaze between their eyes (MGI Ref ID J:3399)
- head spot
- most mice have a white spot on the belly (MGI Ref ID J:3399)
- pallor
- some pups after birth are pale compared to littermates (MGI Ref ID J:3399)
growth/size/body region phenotype
- decreased ear pigmentation
- mice have light ears (MGI Ref ID J:3399)
Genotype: KitlSl/Kitl+
involves: 129/Sv * C3H
endocrine/exocrine gland phenotype
- increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls (MGI Ref ID J:50508)
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers (MGI Ref ID J:50508)
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%) (MGI Ref ID J:50508)
reproductive system phenotype
- increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls (MGI Ref ID J:50508)
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers (MGI Ref ID J:50508)
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%) (MGI Ref ID J:50508)
neoplasm
- increased testicular teratoma incidence
- incidence is 6.92% compared to ~2.6% in controls (MGI Ref ID J:50508)
- percentage is greater in second and subsequent litters compared to first litter or in first litter of older females compared to young mothers (MGI Ref ID J:50508)
- tumors are predominantly in left testis (71%) vs right (27%) or bilateral (2%) (MGI Ref ID J:50508)
- increased tumor incidence
- male mice develop ~2-fold more tumors than controls (MGI Ref ID J:50508)
Genotype: KitlSl/KitlSl
involves: C3H
mortality/aging
- lethality throughout fetal growth and development, complete penetrance
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 (MGI Ref ID J:3399)
- from E14.5-17.5, some embryos show abnormal brain development (3/330) as described in younger embryos (MGI Ref ID J:3399)
- myelencephalic blebs
- one E17.5 embryo displayed a bleb near the midline in the cervical region (MGI Ref ID J:3399)
- spina bifida
- 4/330 embryos aged E14.5-17.5 displayed spina bifida (MGI Ref ID J:3399)
hematopoietic system phenotype
- anemia
- starting around E13.5 and peaking at E14.5, presumed homozygotes display anemia recognized by overall paleness of the embryos (MGI Ref ID J:3399)
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 (MGI Ref ID J:3399)
reproductive system phenotype
- infertility
- mice carrying two mutant alleles are sterile (MGI Ref ID J:5547)
pigmentation phenotype
- absent skin pigmentation
- transplantation of skin grafts from E14, E15 and newborn mutants to normal siblings produced unpigmented hair (MGI Ref ID J:28098)
embryo phenotype
- spina bifida
- 4/330 embryos aged E14.5-17.5 displayed spina bifida (MGI Ref ID J:3399)
integument phenotype
- absent skin pigmentation
- transplantation of skin grafts from E14, E15 and newborn mutants to normal siblings produced unpigmented hair (MGI Ref ID J:28098)
- pallor
- characteristic of anemic embryos (MGI Ref ID J:3399)
Genotype: Krt71Ca/Krt71+
Not Specified
integument phenotype
- curly vibrissae
- curved and irregular in direction (MGI Ref ID J:13054)
- waved hair
- more marked in the first pelage (MGI Ref ID J:13054)
Genotype: Krt71Ca/Krt71Ca
Not Specified
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):2304-9. PubMed: 1559233MGI: 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):234-41. PubMed: 3987963MGI: 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):225-33. PubMed: 1698557MGI: 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):721-33. PubMed: 14573483MGI: J:86407
- Murphy ED. 1977. Effects of mutant steel alleles on leukemogenesis and life-span in the mouse. J Natl Cancer Inst 58(1):107-10. PubMed: 319242MGI: 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):250-4. PubMed: 2460075MGI: J:9423
- Schrott A; Spoendlin H. 1987. Pigment anomaly-associated inner ear deafness. Acta Otolaryngol (Stockh) 103(5-6):451-7. PubMed: 3618172MGI: 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):325-34. PubMed: 688326MGI: 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):213-24. PubMed: 1698556MGI: J:10750
Additional - KitlSl related
- Bennett D. 1956. Developmental analysis of a mutation with pleiotropic effects in the mouse J Morphol 98(2):199-233. MGI: J:28098
- Bernstein SE. 1969. Hereditary disorders of the rodent erythron. In: Genetics in Laboratory Animal Medicine. Natl Acad Sci Publ, Washington, DC. MGI: J:30699
- Chan CK; Chen CC; Luppen CA; Kim JB; DeBoer AT; Wei K; Helms JA; Kuo CJ; Kraft DL; Weissman IL. 2009. Endochondral ossification is required for haematopoietic stem-cell niche formation. Nature 457(7228):490-4. PubMed: 19078959MGI: J:143892
- Chen L; Faire M; Kissner MD; Laird DJ. 2013. Primordial germ cells and gastrointestinal stromal tumors respond distinctly to a cKit overactivating allele. Hum Mol Genet 22(2):313-27. PubMed: 23077213MGI: J:191131
- Chen R; Ning G; Zhao ML; Fleming MG; Diaz LA; Werb Z; Liu Z. 2001. Mast cells play a key role in neutrophil recruitment in experimental bullous pemphigoid. J Clin Invest 108(8):1151-8. PubMed: 11602622MGI: J:72195
- Clark EA; Shultz LD; Pollack SB. 1981. Mutations in mice that influence natural killer (NK) cell activity. Immunogenetics 12(5-6):601-13. PubMed: 6971254MGI: J:6485
- Copeland NG; Gilbert DJ; Cho BC; Donovan PJ; Jenkins NA; Cosman D; Anderson D; Lyman SD; Williams DE. 1990. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell 63(1):175-83. PubMed: 1698554MGI: J:10748
- Deshpande S; Agosti V; Manova K; Moore MA; Hardy MP; Besmer P. 2010. Kit ligand cytoplasmic domain is essential for basolateral sorting in vivo and has roles in spermatogenesis and hematopoiesis. Dev Biol 337(2):199-210. PubMed: 19874813MGI: J:157170
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- Ebihara C; Ebihara K; Aizawa-Abe M; Mashimo T; Tomita T; Zhao M; Gumbilai V; Kusakabe T; Yamamoto Y; Aotani D; Yamamoto-Kataoka S; Sakai T; Hosoda K; Serikawa T; Nakao K. 2015. Seipin is necessary for normal brain development and spermatogenesis in addition to adipogenesis. Hum Mol Genet 24(15):4238-49. PubMed: 25934999MGI: J:226956
- Flanagan JG; Leder P. 1990. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell 63(1):185-94. PubMed: 1698555MGI: J:10749
- Gore BB; Wong KG; Tessier-Lavigne M. 2008. Stem cell factor functions as an outgrowth-promoting factor to enable axon exit from the midline intermediate target. Neuron 57(4):501-10. PubMed: 18304480MGI: J:132880
- Gu Y; Runyan C; Shoemaker A; Surani A; Wylie C. 2009. Steel factor controls primordial germ cell survival and motility from the time of their specification in the allantois, and provides a continuous niche throughout their migration. Development 136(8):1295-303. PubMed: 19279135MGI: J:147283
- Gurish MF; Tao H; Abonia JP; Arya A; Friend DS; Parker CM; Austen KF. 2001. Intestinal mast cell progenitors require CD49dbeta7 (alpha4beta7 integrin) for tissue-specific homing. J Exp Med 194(9):1243-52. PubMed: 11696590MGI: J:119138
- 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):234-41. PubMed: 3987963MGI: J:7810
- Hu B; Colletti LM. 2008. Stem cell factor and c-kit are involved in hepatic recovery after acetaminophen-induced liver injury in mice. Am J Physiol Gastrointest Liver Physiol 295(1):G45-G53. PubMed: 18467506MGI: J:137545
- Ishii M; Tachiwana T; Hoshino A; Tsunekawa N; Hiramatsu R; Matoba S; Kanai-Azuma M; Kawakami H; Kurohmaru M; Kanai Y. 2007. Potency of testicular somatic environment to support spermatogenesis in XX/Sry transgenic male mice. Development 134(3):449-54. PubMed: 17185318MGI: J:135064
- Jones TG; Hallgren J; Humbles A; Burwell T; Finkelman FD; Alcaide P; Austen KF; Gurish MF. 2009. Antigen-induced increases in pulmonary mast cell progenitor numbers depend on IL-9 and CD1d-restricted NKT cells. J Immunol 183(8):5251-60. PubMed: 19783672MGI: J:153832
- Kitamura Y; Go S. 1979. Decreased production of mast cells in S1/S1d anemic mice. Blood 53(3):492-7. PubMed: 367470MGI: J:6084
- Kitamura Y; Yokoyama M; Matsuda H; Shimada M. 1980. Coincidental development of forestomach papilloma and prepyloric ulcer in nontreated mutant mice of W/Wv and SI/SId genotypes. Cancer Res 40(9):3392-7. PubMed: 7000343MGI: J:6393
- Krishnamoorthy N; Oriss TB; Paglia M; Fei M; Yarlagadda M; Vanhaesebroeck B; Ray A; Ray P. 2008. Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthma. Nat Med 14(5):565-73. PubMed: 18454155MGI: J:136704
- Lam MY; Nadeau JH. 2003. Genetic control of susceptibility to spontaneous testicular germ cell tumors in mice. APMIS 111(1):184-90; discussion 191. PubMed: 12752260MGI: J:82965
- Lee DM; Friend DS; Gurish MF; Benoist C; Mathis D; Brenner MB. 2002. Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297(5587):1689-92. PubMed: 12215644MGI: J:78906
- Lotinun S; Evans GL; Turner RT; Oursler MJ. 2005. Deletion of membrane-bound steel factor results in osteopenia in mice. J Bone Miner Res 20(4):644-52. PubMed: 15765184MGI: J:111273
- Lourenssen S; Motro B; Bernstein A; Diamond J. 2000. Defects in sensory nerve numbers and growth in mutant Kit and Steel mice. Neuroreport 11(6):1159-65. PubMed: 10817584MGI: J:103680
- Majumdar MK; Everett ET; Xiao X; Cooper R; Langley K; Kapur R; Vik T; Williams DA. 1996. Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations. Blood 87(8):3203-11. PubMed: 8605335MGI: J:32600
- McCoshen JA; McCallion DJ. 1975. A study of the primordial germ cells during their migratory phase in Steel mutant mice. Experientia 31(5):589-90. PubMed: 1170085MGI: J:5547
- Mikkelsen HB; Malysz J; Huizinga JD; Thuneberg L. 1998. Action potential generation, Kit receptor immunohistochemistry and morphology of steel-Dickie (Sl/Sld) mutant mouse small intestine. Neurogastroenterol Motil 10(1):11-26. PubMed: 9507248MGI: J:113054
- Moro K; Yamada T; Tanabe M; Takeuchi T; Ikawa T; Kawamoto H; Furusawa J; Ohtani M; Fujii H; Koyasu S. 2010. Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463(7280):540-4. PubMed: 20023630MGI: J:156764
- Motro B; Wojtowicz JM; Bernstein A; van der Kooy D. 1996. Steel mutant mice are deficient in hippocampal learning but not long-term potentiation. Proc Natl Acad Sci U S A 93(5):1808-13. PubMed: 8700840MGI: J:32130
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