Overview

Also Known As:flexed tail, dominant spotting

Mutations at the Kit locus affect various aspects of hematopoiesis, the proliferation and migration of primordial germ cells and melanoblasts during development. This double mutant strain carries flexed tail along with the original Kit^W mutation, which is characterized by lethality in most homozygotes with severe macrocytic anemia and a phenotype referred to as 'black-eyed-white' in surviving homozygotes. Heterozygotes have near normal blood parameters with a white belly spot.

Genetic overview

Genetic Background	Generation

f

Allele Type	Gene Symbol	Gene Name
Spontaneous	f	flexed-tail

Kit^W

Allele Type	Gene Symbol	Gene Name
Spontaneous	Kit	KIT proto-oncogene receptor tyrosine kinase

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Research Applications

Hematological Research
Developmental Biology Research
Neurobiology Research
Dermatology Research
Immunology, Inflammation and Autoimmunity Research
Cancer Research
Reproductive Biology Research
Mouse/Human Gene Homologs

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Important Note

This strain is homozygous for f.

Detailed Description

Flexed tail homozygotes can be identified hematologically as earlyas embryonic day 13 and are detectably paler than normal by embryonic day 16, with most paler than normal by embryonic day 15. Homozygotes are small at birth and have a transitory siderocytic hypochromic anemia due to defective heme synthesis in fetal but not adult reticulocytes. Fetal erythrocytes have more alpha hemoglobin synthesis than beta hemoglobin synthesis. Very high numbers of siderocytes are found at birth and this decreases during the first few weeks of life and stabilizes at approximately 3 weeks of age with 3% siderocytes, significantly higher than in wildtype adults. Most homozygotes have a belly spot and 1 to 5 flexures in the tail due to vertebral fusions. Vertebral fusions are also found elsewhere in the vertebral column. Fewer than expected homozygotes are generated indicating prenatal death and the postnatal death rate is approximately 4 times normal. A small minority of homozygotes have been found to have embryonic neural tube defects or a dorsal enlargement of the head.

Development

The FL/1Re inbred strain, homozygous for f and wildtype for Kit, was made from a female WB/Re heterozygous for Kit^W bred to a male heterozygous for f from a partially inbred stock derived from crosses between C3H/J and Snell?s WA linkage-testing stock. The integrated FL/1Re congenic strain, segregating for both Kit^W and f, was derived by repeated backcross-intercross to the developing FL/Re inbred. To generate this FL/1Re segregating congenic a female from the F1 generation of FL/Re heterozygous for Kit^W and homozygous for f was backcrossed to a WC/Re inbred wildtype for both Kit and f and a Kit wildtype f heterozygous offspring was bred to the F2 generation of the incipient FL/1Re inbred (Russell and McFarland, 1966). This strategy of maintenance, backcrossing Kit^W carriers to f/f of the FL/1Re homozygous inbred, was maintained for several decades, with this strain reaching generation N58 in 1974, and in 1980 embryos were generated for cryopreservation from +/+ f/f FL/1Re inbred females at generation F79 and Kit^W/+ f/+ and Kit^W/+ +/+ congenic males at generation N81.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Russell ES; McFarland EC. 1966. Analysis of pleiotropic effects of W and f genic substitutions in the mouse. Genetics 53(5):949-59PubMed: 5929249 MGI: J:24610

View All References

Genetics

f

Allele Symbol: f

Allele Name	flexed tail
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	f, flexed-tail
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	13
General Note	The flexed-tail mutation appeared in a stock maintained by Dr. H.R. Hunt at Michigan State College (J:12951). Homozygotes are small at birth and have a transitory hypochromic, microcytic anemia characterized by a large number of siderocytes containing non-heme iron granules. Most homozygotes also have flexed tail and a belly spot, but these are not constant manifestations of the mutant. Because of the anemia there is probably greater postnatal mortality among f/f than among normal mice (J:14979). The anemia begins on the 12th day of embryonic life when the liver first starts to produce blood cells (J:14979). It is most intense at 15 days of gestation and still severe at birth, but by 2 weeks of age has disappeared. Although adults have normal blood values, their response to hemopoietic stress is defective (J:5439, J:27511). The results of numerous studies have led to the conclusion that the prenatal deficiency in number of erythrocytes and the defective response of adult erythropoietic cells are due to a delay in maturation of already committed erythroid stem cells, and that earlier uncommitted precursors are unaffected by f (J:5439, J:5654, J:5582). An additional effect of f in homozygotes is defective heme synthesis, which occurs in fetal reticulocytes but not in adult reticulocytes nor in erythroblasts at earlier stages of maturation. In fetal reticulocytes there is normal uptake of iron but poor incorporation into hemoglobin (J:5439), probably as a result of reduced activity of delta-aminolevulinate synthetase and dehydratase (J:5591). Fetal erythrocytes of f/f mice have more alpha than beta globin chains. In both f/f and wild-type fetal erythrocytes there is more alpha- than beta-chain mRNA; probably some regulatory mechanism bringing about equal alpha- and beta-chain synthesis exists in wild-type mice but is defective in f/f (J:5827, J:30711). The tail abnormalities are first noticeable on the 14th day of gestation as abnormal differentiation of the intervertebral discs (J:13090). The possibility that abnormal heme synthesis could cause the tail and pigment defects in f/f mice has been discussed (J:5591). It was suggested that flexed-tail might be a mutation in the mouse homolog Fancc of the gene defective in human Fanconi anemia, complementation group C, but no mutation in the Fancc gene or abnormalities in Fancc mRNA have been detected in f/f mutants (J:13598). Also, flexed-tail mice are not susceptible to increases in chromosomal aberrations induced by mitomycin C, a characteristic of Fancc mutant mice (J:35839). This allele arose on a genetically undefined stock in 1927 and was subsequently transferred onto several genetic backgrounds to create the congenic and recombinant inbred lines Je/Le-f/f, FL1/ReJ, WB/ReJ-f/f and C57BL/6J-f/f. The phenotypes listed above might be associated with any of these strains; in most cases it was not specified.
Molecular Note	Note that two conflicting reports (J:68377 and J:98445/J:128616) state that the underlying genetic defect in the flexed tail mouse is either in the Sfxn1 or the Smad5 gene.
Mutations Made By	Mark Fleming, Children's Hospital Boston

Kit^W

Allele Symbol: Kit^W

Allele Name	dominant spotting
Allele Type	Spontaneous
Allele Synonym(s)	W
Gene Symbol and Name	Kit, KIT proto-oncogene receptor tyrosine kinase
Gene Synonym(s)
Strain of Origin	old mutant of the mouse fancy
Chromosome	5
General Note	This is an old mutant of the mouse fancy. Kit^W mutants are a potential model for human inherited pure red cell anemia, called Diamond-Blackfan anemia (OMIM 205900), but mouse mutants do not respond to corticosteroid treatment as do human patients. Thus, the mechanism of anemia causation in the two conditions must be different (J:14286).
Molecular Note	A G-to-A substitution at the first nucleotide at the 5' boundary of intron 10 following the transmembrane exon 10 results in two different aberrantly spliced transcripts putatively expressed in a tissue specific manner. A deletion of 107 bp was found in transcripts from mast cells of mutant mice. A deletion of 234 bp was found in transcripts from brain or bone marrow cells. The mutation disrupts splice donotr site G-GT by changing it to G-AT point, thereby causing exon skipping. The 107 bp deletion could have resulted from skipping of a transmembrane region exon and the 234 bp deletion from skipping 3 exons. The 107 bp deletion would create a frame shift with a stop codon 12 bp downstream, whereas the larger deletion would still be in frame. Northern blot analysis indicated that mast cells from mutants have only 31-37% of the transcripts as mast cells derived from normal bone marrow, suggesting that the mutation may reduce efficiency and authenticity of transcription and splicing.

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

macrocytic anemia

Research Areas By Phenotype

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

Genotype: f related

Hematological Research
- Anemia, Iron Deficiency and Transport Defects
  - microcytic
- Hematopoietic Defects
Developmental Biology Research
- Neural Tube Defects
- Skeletal Defects
Neurobiology Research
- Neural Tube Defects
Dermatology Research
- Color and White Spotting Defects

Genotype: Kit^W related

Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - Mast Cell Deficiency
Cancer Research
- Increased Tumor Incidence
  - Gonadal Tumors
  - Gonadal Tumors: ovarian
- Growth Factors/Receptors/Cytokines
- Oncogenes
Reproductive Biology Research
- Fertility Defects
- Gonadal Tumors
  - ovarian
- Developmental Defects Affecting Gonads
  - germ cell deficient
Mouse/Human Gene Homologs
- piebaldism
- synpolydactyly
Research Tools
- Immunology, Inflammation and Autoimmunity Research
  - Mast Cell Deficiency
Endocrine Deficiency Research
- Skin Defects
- Bone/Bone Marrow Defects
- Gonad Defects
Neurobiology Research
- Receptor Defects
- Hearing Defects
Sensorineural Research
- Retinal Degeneration
- Hearing Defects
Dermatology Research
- Color and White Spotting Defects
Developmental Biology Research
- Neural Crest 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: Kit^W/Kit^W
Not Specified

hematopoietic system phenotype

macrocytic anemia
- macrocytic anemia begins at 12 days gestation leading to death within the first week of birth

integument phenotype

absent coat pigmentation
- white coat color, vividly contrasts with normal black eye color

mortality/aging

postnatal lethality, complete penetrance
- death is within the first week of birth

pigmentation phenotype

abnormal eye pigmentation
- pigment is restricted to retina

absent coat pigmentation
- white coat color, vividly contrasts with normal black eye color

vision/eye phenotype

abnormal eye pigmentation
- pigment is restricted to retina

Genotype: f/f
Not Specified

embryo phenotype

abnormal neural tube morphology
- a minority of homozygotes assessed during embryonic development are found to have irregular lumen shape, longitudinal waves or angles of the tube, or locally doubled neural tube

abnormal notochord morphology
- a minority of homozygotes assessed during embryonic development are found to have ventral swelling of the notochord, dorsal projections, bifurcate notochord, or other morphological abnormalities in the notochord

homeostasis/metabolism phenotype

abnormal iron homeostasis
- defective heme synthesis

integument phenotype

belly spot

limbs/digits/tail phenotype

caudal vertebral fusion
- first appears around E14
- flexure due to unilateral fusions of successive vertebrae

kinked tail
- 1-5 permanent angles in tail
- sometimes curves and spirals instead of sharp angles
- tails can occasionally be nearly normal

mortality/aging

postnatal lethality, incomplete penetrance
- death rate in the first 3 to 4 weeks after birth is about 4 times normal

nervous system phenotype

abnormal neural tube morphology
- a minority of homozygotes assessed during embryonic development are found to have irregular lumen shape, longitudinal waves or angles of the tube, or locally doubled neural tube

pigmentation phenotype

belly spot

skeleton phenotype

abnormal intervertebral disk development
- abnormal development
- fibrous pad sometimes fails to develop or does not develop on one side

abnormal vertebrae morphology

caudal vertebral fusion
- first appears around E14
- flexure due to unilateral fusions of successive vertebrae

vertebral fusion
- fusions seen in caudal vertebrae also seen throughout the vertebral column

growth/size/body region phenotype

abnormal head morphology
- sometimes there is a dorsal enlargement of the head in front of the ears

decreased body size
- smaller size at birth and through adulthood

vision/eye phenotype

eyelids fail to open
- one or both eyes sometimes remain closed

hematopoietic system phenotype

abnormal definitive hematopoiesis
- adults with a poor response to hemopoietic stress
- delayed maturation of committed erythroid stem cells

anemia
- anemia at E14 through birth
- anemia becomes less severe after E16 when hematopoetic function of bone marrow begins
- hematopoesis problem in the liver
- recovery from anemia in the first 2 weeks of life

decreased erythrocyte cell number
- adult RBC counts are normal
- reduced RBC counts from E14 through birth

hypochromic microcytic anemia
- transitory hypochromic and microcytic anemia

Genotype: Kit^W/Kit⁺
Not Specified

integument phenotype

abnormal coat/hair pigmentation

irregular coat pigmentation
- pigmented coat may be interspersed with white hairs creating a roan appearance pigmented areas are interspersed with white hairs producing a roan appearance
- pigmented areas of the coat may be interspersed with white hairs producing a roan appearance pigmented coat may be interspersed with white hairs creating a roan appearance pigmented areas are interspersed with white hairs producing a roan appearance

variable body spotting
- Background Sensitivity - variable amounts of white spotting

mammalian phenotype

hematopoietic system phenotype
- blood parameters are normal

reproductive system phenotype
- system is normal

pigmentation phenotype

abnormal coat/hair pigmentation

irregular coat pigmentation
- pigmented coat may be interspersed with white hairs creating a roan appearance pigmented areas are interspersed with white hairs producing a roan appearance
- pigmented areas of the coat may be interspersed with white hairs producing a roan appearance pigmented coat may be interspersed with white hairs creating a roan appearance pigmented areas are interspersed with white hairs producing a roan appearance

variable body spotting
- Background Sensitivity - variable amounts of white spotting

Genotype: Kit^W/Kit^W
B6.Cg-Kit/J

growth/size/body region phenotype

decreased body weight
- weights are normal at embryonic day 16 but by birth the body weight is retarded behind that of wildtype siblings

hematopoietic system phenotype

macrocytic anemia
- identified as early as embryonic day 16, the earliest timepoint assessed, and the severity is greatest in W/W homozygotes compared with homozygotes for the viable dominant spotting allele or compound heterozgyotes

mortality/aging

abnormal survival
- heterozygous intercrosses produce only 14.5% homozygotes instead of the 25% expected, one sixth of which are born dead or die perinatally and nearly all the remainder die by 3 days of age, without postnatal growth

perinatal lethality, incomplete penetrance

prenatal lethality

The following phenotype relates to a compound genotype created using this strain

Genotype: f/f
FL/1ReJ

growth/size/body region phenotype

decreased body weight
- slight reduction in body weight from birth through 60 days of age in both males and females

hematopoietic system phenotype

decreased erythrocyte cell number
- although red cell counts are significantly reduced at birth they achieve near normal levels by 7 days of age

decreased hematocrit
- at birth the hematocrit is significantly lower (31.5 versus 43.4 in controls) but hematocrit reaches normal levles by 7 days of age

decreased mean corpuscular volume
- significantly smaller volumes at birth but normal by 7 days of age

impaired hematopoiesis
- peak numbers of embryonic erythroid colony forming units only about 50% normal numbers in the liver

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme activity
- delta aminolaevulinate dehydratase activity in embryonic day 17-18 reticulocytes on a per cell basis is appriximately half of that in wild-type controls
- delta aminolaevulinate synthetase activity in embryonic day 16 reticulocytes on a per cell basis is reduced to 53% of that of wild-type controls, and the activity in liver at embryonic day 13-14 is also reduced but to a lesser degree

integument phenotype

white spotting
- white pigment covers an average of 22.9% and 23.6% of the ventrum in females and males respectively

pigmentation phenotype

white spotting
- white pigment covers an average of 22.9% and 23.6% of the ventrum in females and males respectively

Genotype: Kit^W/Kit⁺
FL/1Re-Kit/J

hematopoietic system phenotype

high mean erythrocyte cell number
- elevated from birth onward

increased hematocrit
- slightly elevated from birth onward

References

Russell ES; McFarland EC. 1966. Analysis of pleiotropic effects of W and f genic substitutions in the mouse. Genetics 53(5):949-59PubMed: 5929249 MGI: J:24610

Additional - f related

Additional - Kit^W related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the flexed tail, dominant spotting mouse strain in a publication, please cite the originating article(s) and include JAX stock #000092 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 Kit<W>, Heterozygous or Homozygous for f

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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.

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Also Known As:flexed tail, dominant spotting

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

f

Allele Symbol: f

KitW

Allele Symbol: KitW

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

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

Genotype: f related

Genotype: KitW related

Mammalian Phenotype Terms by Genotype

Genotype: KitW/KitWNot Specified

hematopoietic system phenotype

integument phenotype

mortality/aging

pigmentation phenotype

vision/eye phenotype

Genotype: f/fNot Specified

embryo phenotype

homeostasis/metabolism phenotype

integument phenotype

limbs/digits/tail phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

skeleton phenotype

growth/size/body region phenotype

vision/eye phenotype

hematopoietic system phenotype

Genotype: KitW/Kit+Not Specified

integument phenotype

mammalian phenotype

pigmentation phenotype

Genotype: KitW/KitWB6.Cg-Kit/J

growth/size/body region phenotype

hematopoietic system phenotype

mortality/aging

Genotype: f/fFL/1ReJ

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

integument phenotype

pigmentation phenotype

Genotype: KitW/Kit+FL/1Re-Kit/J

hematopoietic system phenotype

References

Additional - f related

Additional - KitW related

Genotyping Protocols

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

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Kit^W

Allele Symbol: Kit^W

Genotype: Kit^W related

Genotype: Kit^W/Kit^W
Not Specified

Genotype: f/f
Not Specified

Genotype: Kit^W/Kit⁺
Not Specified

Genotype: Kit^W/Kit^W
B6.Cg-Kit/J

Genotype: f/f
FL/1ReJ

Genotype: Kit^W/Kit⁺
FL/1Re-Kit/J

Additional - Kit^W related