Overview

Also Known As:tilted

These mice carry a spontaneous mutation at the Otop1 locus characterized by a head tilt and lack of otoconia in both the utricle and saccule.

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Otop1^tlt

Allele Type	Gene Symbol	Gene Name
Spontaneous	Otop1	otopetrin 1

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Research Applications

Neurobiology 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

Mice homozygous for the Otop1^tlt mutation are viable and fertile. They can be identified outwardly by a tilt in the head posture, which is reported to be detectable in 50-75% of homozygotes. Auditory brainstem responses at four months of age are normal. Although these mice are not deaf and do not show degeneration of the cochlea or vestibular organs, most completely lack otoconia in both the utricle and saccule and thus have problems with spatial orientation. A few giant otoconia have been observed infrequently in a small minority of these mutants, but generally there is agenesis of otoconia. The macular epithelium and otolithic membrane are intact despite the lack of otoconia. Homozygotes are unable to orient themselves in water to find the surface and thus are categorized as non-swimming since they would drown without rescue. Approximately 2% of these homozygotes are able to find the water surface despite somersaults, backflips, or other abnormal motions indicative of failed perception of gravity. Penetrance of the Otop1^tlt mutation is reported to be nearly 100% although there is some variation in expressivity. 2D-PAGE of sensory epithelium and otoconial membrane from Otop1^tlt homozygotes fails to detect otoconin 90, the principal otoconial matrix protein. (Lane 1986 and 1987; Ornitz et al., 1998; Hurle et al., 2001 and 2003.)

Development

The recessive tlt mutation arose spontaneously in 1983 on the STOCK p^6H/p^d background in the laboratory of Eva Eicher at The Jackson Laboratory. Otop1^tlt was backcrossed onto the C57BL/6J background via backcross-intercross. In 1986 C57BL/6J females were bred to homozygous males at NE5F1 and the resulting embryos were cryopreserved.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Otop1^tlt

Allele Symbol: Otop1^tlt

Allele Name	tilted
Allele Type	Spontaneous
Allele Synonym(s)	tilted head; tlt
Gene Symbol and Name	Otop1, otopetrin 1
Gene Synonym(s)
Strain of Origin	STOCK Oca2^p-6H/Oca2^p-d
Chromosome	5
Molecular Note	The mutation in the tlt mouse has been identified as a C-to-A transversion at coding nucleotide 452 in the third exon of the gene. This results in a alanine to glutamic acid change at amino acid position 151 (p.A151E).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Otop1^tlt related

Neurobiology Research
- Vestibular Defects
Sensorineural Research
- Vestibular 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: Otop1^tlt/Otop1^tlt
STOCK Oca2/Oca2

behavior/neurological phenotype

abnormal posture
- mice tuck the head towards the belly when picked up by the tail

head tilt
- mice often hold head in tilted position

impaired swimming
- mice cannot swim

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

Genotype: Otop1^tlt/Otop1^tlt
B6.Cg-Otop1/J

behavior/neurological phenotype

head tilt
- observed in 50-75% of homozygous mice

impaired swimming
- a small number of homozygotes could keep the nose but not the tail out of water; a few others could sometimes find the water surface but occasionally required rescuing
- when dropped into a tank of water, most homozygous mice spiral immediately downward and require rescuing

nervous system phenotype

abnormal vestibular ganglion morphology
- morphometric analysis of the total vestibular ganglion volume and total cellular volume shows that mutants have reduced levels and developed slower than controls in the first 12 days of postnatal life

hearing/vestibular/ear phenotype

absent linear vestibular evoked potential
- absent vestibular nerve compund action potentials in response to linear acceleration at 9 and 16 pulses/s

absent otoliths
- complete absence of otoconia from the saccule and the utricle is observed at 3-5 weeks of age as well as E17.5 and newborn homozygous mice
- in the rare mice that show a partial ability to swim, either otoconia are completely absent, or one or more giant otoconia are seen in the saccule

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - histological analysis shows a grossly normal appearance of the middle ear and the bony and membranous labyrinths
- Normal - mice do not appear to have any hearing loss; ABR threshold determination shows similar levels compared to controls for all sound pressure levels tested
- Normal - the cochlear duct, including the sensory and suppporting cells, cochlear nerve fibers and the tectorial membrane all appear similar to controls
- Normal - the sensory epithelia and otoconial membranes appear similar to controls; the otolithic membrane is visible over the surface of the maculae and there is no significant difference in the density of hair cells in the saccular and utricular maculae

References

Additional References

Hurle B; Ignatova E; Massironi SM; Mashimo T; Rios X; Thalmann I; Thalmann R; Ornitz DM. 2003. Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1. Hum Mol Genet 12(7):777-89PubMed: 12651873 MGI: J:82639
Hurle B; Lane K; Kenney J; Tarantino LM; Bucan M; Brownstein BH; Ornitz DM. 2001. Physical Mapping of the Mouse Tilted Locus Identifies an Association between Human Deafness Loci DFNA6/14 and Vestibular System Development. Genomics 77(3):189-99PubMed: 11597144 MGI: J:72229
Jones SM; Erway LC; Johnson KR; Yu H; Jones TA. 2004. Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191(1-2):34-40PubMed: 15109702 MGI: J:89392
Ornitz DM; Bohne BA; Thalmann I; Harding GW; Thalmann R. 1998. Otoconial agenesis in tilted mutant mice. Hear Res 122(1-2):60-70PubMed: 9714575 MGI: J:49524

Additional - Otop1^tlt related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Otop1
- Genotyping resources and troubleshooting
Appearance
- black
  Related Genotype: a/a
Citation
When using the tilted mouse strain in a publication, please cite the originating article(s) and include JAX stock #001104 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 Otop1<tlt>

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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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Licensing Information

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Also Known As:tilted

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Otop1tlt

Allele Symbol: Otop1tlt

Disease Terms

Research Areas By Phenotype

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

Genotype: Otop1tlt related

Mammalian Phenotype Terms by Genotype

Genotype: Otop1tlt/Otop1tltSTOCK Oca2/Oca2

behavior/neurological phenotype

Genotype: Otop1tlt/Otop1tltB6.Cg-Otop1/J

behavior/neurological phenotype

nervous system phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

References

Additional References

Additional - Otop1tlt related

Genotyping Protocols

Appearance

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

Otop1^tlt

Allele Symbol: Otop1^tlt

Genotype: Otop1^tlt related

Genotype: Otop1^tlt/Otop1^tlt
STOCK Oca2/Oca2

Genotype: Otop1^tlt/Otop1^tlt
B6.Cg-Otop1/J

Additional - Otop1^tlt related