Description

Strain Information

Former Names B6Ei.GL-het/J    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Heterozygote x Homozygote         (Female x Male) Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Background Strain C57BL/6JEiJ Donor Strain GL/LE Generation N10F14+N3F4 (06-DEC-07)

Appearance
black, head tilt
Related Genotype: a/a Nox3^het/Nox3^het

black, unaffected
Related Genotype: a/a Nox3^het/+ or a/a ?/+

Description
Head tilt (het) is an autosomal recessive mutation that can cause abnormal circling behavior and hyperactivity in affected mice. Homozygotes also exhibit a subtle head tilt. Together, the abnormal behavioral phenotype is consistent with that of a vestibular disorder. Evoked auditory brainstem response profiles are normal indicating that the mutants are not deaf. het/het mutants are unable to sense orientation under water and therefore, cannot swim properly. If held by the tail, het/het mice retract, rather than extend, their limbs; they also flex ventrally, instead of dorsally as wild type mice do. When lowered quickly by the tail, het/het mice fail to extend their forelimbs in a normal manner and have difficulty righting themselves if dropped vertically from a short distance. Morphological assessment of the inner ear of homozygotes reveals an abnormal appearance of the saccule and utricle owing to a complete absence of otoliths. Otoliths are tiny calciferous granules within the statoconic membrane that covers the sensory epithelia of the acoustic maculae. These ear crystals function as mass particles that stimulate gravity receptors in the maculae of the utricle and saccule in response to head tilting and gravitational forces. Electrophysiological assessment of the vestibular neurons in the het mutants demonstrates these cells totally lack vestibular evoked potentials in response to pulsed linear acceleration. Thus, the mutants are unable to process ostolite-mediated sensory stimuli throughout their entire lifespan. The het gene product is likely involved in the formation of the otolithic ear crystals (prior to embryonic day 14), perhaps through the regulation of calcium secretion by neuroepithelial cells. Structures of the cochlea and middle ear appear normal and melanocyte function is not compromised. (Sweet, 1980; Bergstrom et al., 1998; Jones et al., 1999)

Development
The het mutation arose spontaneously at The Jackson Laboratory in 1975 in the GL/Le inbred strain (Stock No. 000255) which was then at F25. In 1976, a male het/het (F27) was outcrossed once to the F1 hybrid C3B6A/A^w-J to separate het from downless Jackson (Edar^dl-J) and grey lethal (gl). The strain was maintained by sibling mating thereafter. gl and Edar^dl-J have not been detected in the stock since F2. The het mutation was backcrossed from the C3B6-A/A^w-J background onto C57BL/6JEi reaching N10F14+N2F12 in 2002.

Control Information

	Control
	Heterozygote from the colony
	Untyped from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Nox3^het allele

000061

B6 x STOCK Nox3het/J

View Strains carrying   Nox3^het     (1 strain)

Strains carrying other alleles of Nox3

003483	B6 x B10.D1-H2q/SgJ-Nox3het-2J/J
005014	C57BL/6J-Nox3het-4J/J

View Strains carrying other alleles of Nox3     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Nox3^het/Nox3^het

        C57BL/6JEi

• adipose tissue phenotype
• decreased adipose tissue amount (MGI Ref ID J:88596)
  • percent lean mass was significantly higher in mutants
  • percent lean mass did not differ significantly between 1G and 2G mutants
  • percent body fat was significantly lower in mutants
  • percent body fat did not differ significantly between 1G and 2G mutants
• behavior/neurological phenotype
• abnormal circadian rhythm (MGI Ref ID J:88596)
  • the amplitude of body temperature circadian rhythm was significantly larger in mutants
  • this is largely attributable to lower mean resting body temperature in mutants
  • the amplitude of activity circadian rhythm was significantly larger in mutants
• abnormal food intake (MGI Ref ID J:88596)
  • the decrease in food intake following onset of 2G is smaller and delayed in mutants than in wildtypes
  • under normal (1G) conditions food intake does not differ between mutants and wild-types
• absent vestibuloocular reflex (MGI Ref ID J:83379)
  • the mutants exhibit almost no or highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate both the otoliths and semicircular canals (vestibulo ocular reflex)
  • the mutants exhibit highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate only the only semicircular canals
  • in both cases the response of these mutants is less at lower rotational frequencies
  • these results suggest these mutants lack canal mediated vestibulo ocular reflex and have deficient semicircular canal mediated vestibulo ocular reflex
• altered righting response (MGI Ref ID J:59485)
  • young mutant pups (1 - 3 weeks old) had difficulty rolling over and righting when disturbed
• head tilt (MGI Ref ID J:59485)
• impaired swimming (MGI Ref ID J:88596)
  • mutants are unable to swim or float
• growth/size phenotype
• decreased body weight (MGI Ref ID J:88596)
  • the body mass of mutants is slightly less than that of wild-types
  • the drop in body mass following onset of 2G is significantly less for mutants than wild-types
  • the drop in body mass for mutants following onset of 2G is transient and not significantly different from 1G controls while the drop in body mass for wild-types is sustained and significantly different from 1G controls
• hearing/vestibular/ear phenotype
• absent linear vestibular evoked potential (MGI Ref ID J:59485)
  • mutants have no measurable vestibular evoked potential in response to linear acceleration
• absent otoliths (MGI Ref ID J:59485)
  • the otoliths are bilaterally absent
  • mutants displayed normal response to auditory stimuli
• absent vestibuloocular reflex (MGI Ref ID J:83379)
  • the mutants exhibit almost no or highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate both the otoliths and semicircular canals (vestibulo ocular reflex)
  • the mutants exhibit highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate only the only semicircular canals
  • in both cases the response of these mutants is less at lower rotational frequencies
  • these results suggest these mutants lack canal mediated vestibulo ocular reflex and have deficient semicircular canal mediated vestibulo ocular reflex
• head tilt (MGI Ref ID J:59485)
• homeostasis/metabolism phenotype
• abnormal body temperature regulation (MGI Ref ID J:88596)
  • at the onset of 2G mutants do not have a large drop in body temperature unlike wild-types

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Nox3^het/Nox3^het

        GL/Le

• behavior/neurological phenotype
• circling (MGI Ref ID J:13861)
• head tilt (MGI Ref ID J:13861)
• hyperactivity (MGI Ref ID J:13861)
• impaired swimming (MGI Ref ID J:13861)
• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:13861)
  • mutants are not deaf
• circling (MGI Ref ID J:13861)
• head tilt (MGI Ref ID J:13861)

Nox3^het/Nox3^het

        C57BL/6J

• behavior/neurological phenotype
• circling (MGI Ref ID J:50247)
  • increased rarity of circling behaviour in mutants from The Jackson Laboratory compared to those from Harwell possibly as a result of differences in background
• head tilt (MGI Ref ID J:50247)
• impaired swimming (MGI Ref ID J:50247)
• hearing/vestibular/ear phenotype
• absent otoliths (MGI Ref ID J:50247)
  • the otoliths are bilaterally absent
  • no other inner ear abnormalities were found
  • mutants displayed normal response to auditory stimuli
• circling (MGI Ref ID J:50247)
  • increased rarity of circling behaviour in mutants from The Jackson Laboratory compared to those from Harwell possibly as a result of differences in background
• head tilt (MGI Ref ID J:50247)

View Research Applications

Research Applications

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

Nox3^het related

Neurobiology Research
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Nox3het
Allele Name		head-tilt
Allele Type		Spontaneous
Common Name(s)		het;
Strain of Origin		GL/Le
Gene Symbol and Name		Nox3, NADPH oxidase 3
Chromosome		17
Gene Common Name(s)		GP91-3; head-tilt; het; neuroscience mutagenesis facility, 250; nmf250;
Molecular Note		The mutation in the het mouse was identified as retroviral insertion into intron 12, resulting in aberrant splicing. [MGI Ref ID J:89010]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Bergstrom RA; You Y; Erway LC; Lyon MF; Schimenti JC. 1998. Deletion mapping of the head tilt (het) gene in mice: a vestibular mutation causing specific absence of otoliths. Genetics 150(2):815-22. [PubMed: 9755211]  [MGI Ref ID J:50247]

Fuller PM; Jones TA; Jones SM; Fuller CA. 2002. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection? Proc Natl Acad Sci U S A 99(24):15723-8. [PubMed: 12434016]  [MGI Ref ID J:88596]

Jones SM; Erway LC; Bergstrom RA; Schimenti JC; Jones TA. 1999. Vestibular responses to linear acceleration are absent in otoconia-deficient C57BL/6JEi-het mice. Hear Res 135(1-2):56-60. [PubMed: 10491954]  [MGI Ref ID J:59485]

Nox3^het related

Bergstrom RA; You Y; Erway LC; Lyon MF; Schimenti JC. 1998. Deletion mapping of the head tilt (het) gene in mice: a vestibular mutation causing specific absence of otoliths. Genetics 150(2):815-22. [PubMed: 9755211]  [MGI Ref ID J:50247]

Fuller PM; Jones TA; Jones SM; Fuller CA. 2002. Neurovestibular modulation of circadian and homeostatic regulation: vestibulohypothalamic connection? Proc Natl Acad Sci U S A 99(24):15723-8. [PubMed: 12434016]  [MGI Ref ID J:88596]

Harrod CG; Baker JF. 2003. The vestibulo ocular reflex (VOR) in otoconia deficient head tilt (het) mutant mice versus wild type C57BL/6 mice. Brain Res 972(1-2):75-83. [PubMed: 12711080]  [MGI Ref ID J:83379]

Hoffman LF; Ross MD; Varelas J; Jones SM; Jones TA. 2006. Afferent synapses are present in utricular hair cells from otoconia-deficient mice. Hear Res 222(1-2):35-42. [PubMed: 17023128]  [MGI Ref ID J:115261]

Jones SM; Erway LC; Bergstrom RA; Schimenti JC; Jones TA. 1999. Vestibular responses to linear acceleration are absent in otoconia-deficient C57BL/6JEi-het mice. Hear Res 135(1-2):56-60. [PubMed: 10491954]  [MGI Ref ID J:59485]

Lyon MF; Schimenti JC; Evans EP. 2000. Narrowing the critical regions for mouse t complex transmission ratio distortion factors by use of deletions Genetics 155(2):793-801. [PubMed: 10835400]  [MGI Ref ID J:62655]

Paffenholz R; Bergstrom RA; Pasutto F; Wabnitz P; Munroe RJ; Jagla W; Heinzmann U; Marquardt A; Bareiss A; Laufs J; Russ A; Stumm G; Schimenti JC; Bergstrom DE. 2004. Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev 18(5):486-91. [PubMed: 15014044]  [MGI Ref ID J:89010]

Sweet HO. 1980. Head tilt (het) Mouse News Lett 63:19.  [MGI Ref ID J:13861]

Xue B; Skala K; Jones TA; Hay M. 2004. Diminished baroreflex control of heart rate responses in otoconia-deficient C57BL/6JEi head tilt mice. Am J Physiol Heart Circ Physiol 287(2):H741-7. [PubMed: 15059776]  [MGI Ref ID J:95596]

Zhao X; Jones SM; Yamoah EN; Lundberg YW. 2008. Otoconin-90 deletion leads to imbalance but normal hearing: a comparison with other otoconia mutants. Neuroscience 153(1):289-99. [PubMed: 18355969]  [MGI Ref ID J:136073]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           A1

Colony Maintenance

Mating System	Heterozygote x Homozygote         (Female x Male)
	Heterozygote x Heterozygote         (Female x Male)

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Heterozygote from the colony
	Untyped from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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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.

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