Overview

Also Known As:flexed tail

It has not been conclusively determined if f is an allele of Sfxn1, for this reason we have renamed the allele identified by Dr. Fleming from f to Sfxn1^m1Mdf. The strain currently exhibits a flexed tail phenotype; it is not known if the phenotypic flexed tail will be eliminated when the colony is maintained by genotype rather than phenotype.

Donating Investigator

Mark D Fleming, Children's Hospital Boston

Genetic overview

Genetic Background	Generation

Sfxn1^m1Mdf

Allele Type	Gene Symbol	Gene Name
Spontaneous	Sfxn1	sideroflexin 1

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Research Applications

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Details

Detailed Description

NOTE: It has not been conclusively determined if f is an allele of Sfxn1, for this reason we have renamed the allele identified by Dr. Fleming from f to Sfxn1^m1Mdf. The strain currently exhibits a flexed tail phenotype; it is not known if the phenotypic flexed tail will be eliminated when the colony is maintained by genotype rather than phenotype.

That said -- the following describes the flexed tail phenotype --- Mice homozygous for the flexed-tail (f) allele can be identified hematologically as early as embryonic day 13 and are detectably paler than normal by embryonic day 16. Homozygotes are small at birth and have a transitory siderocytic hypochromic anemia due to defective heme synthesis in fetal, but not adult reticulocytes. 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 that the 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 flexed tail (f) mutation arose spontaneously on an undefined mouse stock in the laboratory of Dr. Harrison Hunt at Michigan State College in 1927. The strain has been introgressed into multiple backgrounds including FL/1ReJ, JE/LeJ, and WB. Mapping work done by Dr. Mark Fleming suggests that f is a single base insertion (adenine) in exon 2 of the sideroflexin 1 (Sfxn1) gene, which results in a truncated peptide. Western blot analysis indicates that protein is absent. Concurrently, another group has identified f as a mutation in Smad5. Dr Fleming at Harvard Medical College backcrossed the Sfxn1^m1Mdf allele to 129S6/SvEvTac for a minimum of 19 generations.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Fleming MD; Campagna DR; Haslett JN; Trenor CC 3rd; Andrews NC. 2001. A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice. Genes Dev 15(6):652-7PubMed: 11274051 MGI: J:68377

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Genetics

Sfxn1^m1Mdf

Allele Symbol: Sfxn1^m1Mdf

Allele Name	mutation 1, Mark Fleming
Allele Type	Spontaneous
Allele Synonym(s)	f
Gene Symbol and Name	Sfxn1, sideroflexin 1
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	13
General Note	This allele is on of two suggested as responsible for the flexed tail mutation (f). J:128616 suggests that a Smad5 splicing defect (mutation in a polyT element in intron 4) may be causative of flexed tail.
Molecular Note	An insertion of a single A residue after codon 15 of the reading frame. This mutation is predicted to result in a truncated protein consisting of the first 15 amino acids followed by 17 novel amino acids before an in-frame stop codon.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

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

Genotype: f/f
Not Specified

homeostasis/metabolism phenotype

abnormal iron homeostasis
- defective heme synthesis

integument phenotype

belly spot

embryo phenotype

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

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

limbs/digits/tail phenotype

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

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

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 vertebrae morphology

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

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

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

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

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

hypochromic microcytic anemia
- transitory hypochromic and microcytic anemia

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

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

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

homeostasis/metabolism phenotype

abnormal enzyme/coenzyme activity
- 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
- delta aminolaevulinate dehydratase activity in embryonic day 17-18 reticulocytes on a per cell basis is appriximately half of that in wild-type controls

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: f/f
involves: CBA/St

mortality/aging

postnatal lethality, incomplete penetrance
- early postnatal depletion of homozygous animals

hematopoietic system phenotype

anemia
- first evident at embryonic day 12

reticulocytosis
- striking reticulocytosis at birth and reticulocyte count remains high at 13 days of age but decreases by 3 weeks of age as the anemia resolves

hypochromic anemia
- although the mean red blood cell size is normal, the hemoglobin concentration is reduced, there are fewer red blood cells and this transitory anemia is most significant embryonically and at birth then wanes during the first few weeks of life

increased siderocyte number
- the percentage of siderocytes decreases from 80% at birth to approximately 40% at 1 week of age and stabilizes at approximately 3% by 3 weeks of age persisting at this higher than normal level in the adult
- the majority of red blood cells in newborns are siderocytes, which are incompletely haemoglobinized as evidenced by faint color and weak stain uptake

decreased mean corpuscular hemoglobin

integument phenotype

pallor
- homozygotes are recognizably paler than normal from embryonic day 16 onward and most can be identified this way as early as embryonic day 15

References

Fleming MD; Campagna DR; Haslett JN; Trenor CC 3rd; Andrews NC. 2001. A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice. Genes Dev 15(6):652-7PubMed: 11274051 MGI: J:68377

Additional - Sfxn1^m1Mdf related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Pyrosequencing:Cg-f-PYRO
- Genotyping resources and troubleshooting
Breeding Considerations

The donating investigator maintains this as a backcross/intercross (hom x 129S6, het x het) mating.
- Additional Breeding and Husbandry Support
Citation
When using the flexed tail mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36656 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:flexed tail

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Sfxn1m1Mdf

Allele Symbol: Sfxn1m1Mdf

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: f/fNot Specified

homeostasis/metabolism phenotype

integument phenotype

embryo 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: f/fFL/1ReJ

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

integument phenotype

pigmentation phenotype

Genotype: f/finvolves: CBA/St

mortality/aging

hematopoietic system phenotype

integument phenotype

References

Additional - Sfxn1m1Mdf related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Sfxn1^m1Mdf

Allele Symbol: Sfxn1^m1Mdf

Genotype: f/f
Not Specified

Genotype: f/f
FL/1ReJ

Genotype: f/f
involves: CBA/St

Additional - Sfxn1^m1Mdf related