Overview

Also Known As:hyperspin

This 123.6 kb intragenic deletion appears to include a regulatory sequence that controls Dlx5 expression at least in the otocyst so this mutant provides a model of split-hand/foot malformation 1 (SHFM1) without craniofacial defects and a model with which to dissect the regulation of the genomic region that includes Dlx5 and Slc25a13.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Slc25a13^hspn

Allele Type	Gene Symbol	Gene Name
Spontaneous (Null/Knockout, Dominant negative)	Slc25a13	solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13

Marker(s)

	Marker Symbol	Marker Name
	Dlx5	distal-less homeobox 5

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Research Applications

Developmental Biology Research
Sensorineural Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The hyperspin mutation is a spontaneous 123.6 kb deletion that begins in intron 3 of Slc25a13 and ends in exon 17, an interval that includes an enhancer of Dlx5. This deletion includes the putative enhancer elements hs2313 and hs1642, and overlaps the regions corresponding to the predicted intervals of split-hand/foot malformation (SHFM) and split-hand/foot malformation with hearing loss (SHFM & HL) sub-regions of the SHFM1 locus, but not the split-hand/foot malformation with hearing loss and craniofacial abnormalities (SHFM & HL & CF) sub-region. Hyperspin homozygotes exhibit the phenotypes indicative of a vestibular defect, rapid circling, head shaking, and failure to orient in water, but null alleles in Slc25a13 have not been found to cause vestibular defects. At 4 to 5 weeks of age homozygotes were found to be deaf by ABR analysis. At 5 weeks of age the inner ears of homozygotes are small and malformed, the cochlea has too few turns and appears swollen, and the three semicircular canals are absent, reduced, or malformed. At embryonic day 15.5 the endolymphatic duct and sac and the superior and posterior semicircular canals are missing, the cochlear duct is wider and has fewer coils than normal, and most homozygotes also lack the lateral semicircular canal and utricle. Scanning electron microscopy of the basal and middle turns of the cochlea at 4 weeks of age revealed only occasional missing hair bundles, but the apical turn had an additional forth and sometimes fifth row of outer hair cells and abnormal hair bundle orientations. Only approximately 30% of female and 50% of male hyperspin homozygotes survive to wean age. Hyperspin homozygotes have reduced otocyst expression but not branchial arch expression of Dlx5, a gene more than 600 kb away on Chromosome 6, and null alleles of Dlx5 have been found to cause perinatal death, dysmorphic inner ears and other craniofacial abnormalities. While hyperspin heterozygotes have a normal phenotype fewer than 10% of Slc25a13^hspn Dlx5⁺/Slc25a13⁺ Dlx5^{tm1(cre/ERT2)Zjh} transchromosomal heterozygotes survive to wean age, a more severe phenotype than that of hyperspin homozygotes and further proof of the presence of a Dlx5 modifier within the hyperspin deletion. These double heterozygotes display circling and head bobbing, are deaf by ABR, and have malformed inner ears similar to that found in hyperspin homozygotes.

To identify the sequence within the hyperspin deletion that regulates Dlx5 otic expression, endonuclease-mediated deletions were generated of hs2313 in intron 14, hs1642 in intron 3, and intron 3 through 4. None of these caused the phenotype found in hyperspin homozygotes, even when Dlx5^{tm1(cre/ERT2)Zjh} transchromosomal heterozygotes were generated.

Development

The hyperspin deletion arose spontaneously in the CXJ1/SalkJ strain at The Jackson Laboratory and it was later determined that the mutation arose in SLJ/J-derived sequence. This mutation was moved onto the C57BL/6J background by repeated backcross-intercross breeding until generation N10 when sibling intercrossing of heterozygous females with homozygous males began. Embryos were cryopreserved from C57BL/6J females bred to homozygous males at generation N10F3.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Johnson KR; Gagnon LH; Tian C; Longo-Guess CM; Low BE; Wiles MV; Kiernan AE. 2018. Deletion of a Long-Range Dlx5 Enhancer Disrupts Inner Ear Development in Mice. Genetics 208(3):1165-1179PubMed: 29301908 MGI: J:254776

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Genetics

Slc25a13^hspn

Allele Symbol: Slc25a13^hspn

Allele Name	hyperspin
Allele Type	Spontaneous (Null/Knockout, Dominant negative)
Allele Synonym(s)
Gene Symbol and Name	Slc25a13, solute carrier family 25 (mitochondrial carrier, adenine nucleotide translocator), member 13
Gene Synonym(s)
Strain of Origin	SJL/J
Chromosome	6
Molecular Note	The hyperspin mutation is a spontaneous 123.6 kb deletion of Chromosome 6: 5.86-6.66 Mb (GRCm38) that begins in intron 3 of Slc25a13 and ends in exon 17, an interval that includes an enhancer of Dlx5 and, in addition to creating a null allele of Slc25a13, diminishes otocyst expression of Dlx5.

Dlx5

Marker Symbol: Dlx5

Marker Synonym(s)
Chromosome(s)	6

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Slc25a13^hspn related

Developmental Biology Research
- Postnatal Lethality
  - Homozygous
Sensorineural Research
- Hearing Defects
- Vestibular Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Slc25a13^hspn/Slc25a13^hspn
B6.SJL(C)-Slc25a13/Kjn

behavior/neurological phenotype

circling
- rapid circling

head shaking

impaired swimming
- fail to orient in water

nervous system phenotype

abnormal cochlear hair cell morphology
- at 4 weeks of age there are only occassional missing hair bundles throughout the basal and middle turns of the cochlea, but there is an additional 4th or sometimes 5th row of outer hair cells in the apical turn where there can also be abnomral orientation of hair bundles

hearing/vestibular/ear phenotype

abnormal cochlea morphology

abnormal cochlear hair cell morphology
- at 4 weeks of age there are only occassional missing hair bundles throughout the basal and middle turns of the cochlea, but there is an additional 4th or sometimes 5th row of outer hair cells in the apical turn where there can also be abnomral orientation of hair bundles

abnormal inner ear morphology
- at 5 weeks of age the inner ears are small and malformed, the cochlea has fewer turns than normal and appears swollen, all 3 semicircular canals are either absent, smaller, or malformed

abnormal lateral semicircular canal morphology
- absent in 6 of 7 embryos assessed at E15.5

abnormal posterior semicircular canal morphology

abnormal scala media morphology

abnormal semicircular canal morphology
- all 3 semicircular canals are either absent, reduced or malformed

abnormal superior semicircular canal morphology

absent endolymphatic duct
- embryonic day 15.5 absent in all of 7 embryos

absent endolymphatic sac
- embryonic day 15.5 absent in all of 7 embryos

absent semicircular canals

absent utricle
- absent in 6 of 7 embryos at E15.5

deafness

decreased cochlear coiling

increased or absent threshold for auditory brainstem response
- at 4 to 5 weeks of age no ABR wave patterns detectable for pure tone 8, 16, or 32 kHz even at 100 dB

References

Johnson KR; Gagnon LH; Tian C; Longo-Guess CM; Low BE; Wiles MV; Kiernan AE. 2018. Deletion of a Long-Range Dlx5 Enhancer Disrupts Inner Ear Development in Mice. Genetics 208(3):1165-1179PubMed: 29301908 MGI: J:254776

Additional - Dlx5 related

Additional - Slc25a13^hspn related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Genotyping resources and troubleshooting
Citation
When using the hyperspin mouse strain in a publication, please cite the originating article(s) and include JAX stock #005679 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 for Slc25a13<hspn>

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Also Known As:hyperspin

Genetic overview

Marker(s)

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Slc25a13hspn

Allele Symbol: Slc25a13hspn

Dlx5

Marker Symbol: Dlx5

Disease Terms

Research Areas By Phenotype

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

Genotype: Slc25a13hspn related

Mammalian Phenotype Terms by Genotype

Genotype: Slc25a13hspn/Slc25a13hspnB6.SJL(C)-Slc25a13/Kjn

behavior/neurological phenotype

nervous system phenotype

hearing/vestibular/ear phenotype

References

Additional - Dlx5 related

Additional - Slc25a13hspn 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

Slc25a13^hspn

Allele Symbol: Slc25a13^hspn

Genotype: Slc25a13^hspn related

Genotype: Slc25a13^hspn/Slc25a13^hspn
B6.SJL(C)-Slc25a13/Kjn

Additional - Slc25a13^hspn related