Overview

Also Known As:hypophosphatemia Duke

These mice carry a spontaneous mutation at the Phex locus characterized by low level of serum phosphorus, skeletal defects, and behavior consistent with vestibular dysfunction. This mutant offers a model for X-linked dominant hypophosphatemic rickets.

Genetic overview

Genetic Background	Generation

Phex^Hyp-Duk

Allele Type	Gene Symbol	Gene Name
Spontaneous	Phex	phosphate regulating endopeptidase homolog, X-linked

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

This mutant offers a model for X-linked dominant hypophosphatemic rickets. The serum phosphorus (2.95 mg/dL) in hemizygous males is lower than that found in hypophosphatemia, hypophosphatemia 2 Jackson, or gyro hemizygous males. The skeletal defects include shortened long bones and craniofacial defects and hemizygous males have cochlear degeneration and a heightened auditory brainstem response threshold, higher than that in other Phex mutants. The heightened ABR threshold is dependent upon a modifier that is absent in BALB/cByJ. Consistent with vestibular dysfunction, approximately half of the hemizygous males and some of the heterozygous females display circling behavior, and in hemizygous males head bobbing or unstable gait have also been noted. Hemizygous males are mildly growth retarded, with a squared and shortened body, and shortened hind limbs and tail. While some heterozygous females display circling and growth retardation, not all do and they are more difficult to distinguish from wildtype than are heterozygous hypophosphatemia 2 Jackson heterozygotes.

Development

The Hyp-Duk mutation arose spontaneously in a BALB/cAnBomUrd subline bearing a nude (Foxn1) mutation in the laboratory of Susan Poulton at Duke University. In Sept 1998 BALB/AnBomUrd mice segregating for both nude and the Hyp-Duk mutation at generation F64 were received at The Jackson Laboratory, sibling bred, and re-derived. Through selective sibling crosses the nude mutation was bred out of this strain and the Hyp-Duk mutation maintained. The strain continued to be maintained through sibling inbreeding.

Control Suggestions

Wild-type from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Lorenz-Depiereux B; Guido VE; Johnson KR; Zheng QY; Gagnon LH; Bauschatz JD; Davisson MT; Washburn LL; Donahue LR; Strom TM; Eicher EM. 2004. New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. Mamm Genome 15(3):151-61PubMed: 15029877 MGI: J:88352

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Genetics

Phex^Hyp-Duk

Allele Symbol: Phex^Hyp-Duk

Allele Name	hypophosphatemia, Duke
Allele Type	Spontaneous
Allele Synonym(s)
Gene Symbol and Name	Phex, phosphate regulating endopeptidase homolog, X-linked
Gene Synonym(s)
Strain of Origin	CAnBomUrd.Cg-Foxn1^nu
Chromosome	X
Molecular Note	Genomic PCR and Southern blot analysis indicated a deletion of at least 30 kb containing exons 13 and 14 of the Phex gene.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

X-linked dominant hypophosphatemic rickets

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

otitis media

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: Phex^Hyp-Duk/Y
B6.C-Phex/J

craniofacial phenotype

abnormal cranium morphology
- slightly abnormal shape

growth/size/body region phenotype

decreased body size

hearing/vestibular/ear phenotype

abnormal otic capsule morphology
- by one month of age the otic capsule is markedly thickened and surrounded by non-mineralized bone, similar to that seen on the BALB/cUrd background

increased or absent threshold for auditory brainstem response
- Background Sensitivity - although on the C67BL/6J background the ABR threshold is normal in younger mice, at over 2 months of age some unilateral increase in threshold of 10-15 dB SPL above normal is found so the hearing loss is much less severe than on the BALB/cUrd background

mammalian phenotype

behavior/neurological phenotype
- Background Sensitivity - startle response is normal and no head-bobbing or circling are seen

hearing/vestibular/ear phenotype
- Background Sensitivity - ABR recordings at 21 to 50 days of age are normal, cochlear ducts at 4 months of age do not show endolymphatic hydrops or spiral ganglion cell degeneration
- Background Sensitivity - startle response is normal and no head-bobbing or circling are seen

skeleton phenotype

abnormal cranium morphology
- slightly abnormal shape

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

Genotype: Phex^Hyp-Duk/Y
involves: BALB/cAnBomUrd

adipose tissue phenotype

decreased total body fat amount
- a significant increase in lean body mass is seen compared to controls

growth/size/body region phenotype

decreased body weight
- all males have significantly lower body weights, ~25% less than controls

postnatal growth retardation
- all males are mildly growth retarded in overall body size with a squared trunk

hearing/vestibular/ear phenotype

abnormal cochlea morphology
- endolymph volume appears larger in the cochleas, resulting in increased scala media, decreased scala vestibule and displacement of Reissner's membrane which separates these

abnormal inner ear morphology

abnormal otic capsule morphology
- the otic bony capsule of hemizygotes is thickened and surrounded by non-mineralized bone at around 25 days of age

abnormal scala tympani morphology
- a precipitate is found in the scala tympani of the cochlea

abnormal vestibular saccule morphology
- in some instances at 90 days of age the saccule is ruptured apparently due to hydrops

distended Reissner membrane

ear inflammation
- by 40 days of age most hemizygotes have severe endolymphatic hydrops with distension of Reissner's membrane
- by 90 days of age severe hydrops in all parts of the labyrinth is found and Reissner's membrane is displaced
- some hemizygotes show mild apical hydrops at 21 to 25 days of age, but this is not accompanied by hair cell loss and the endolymphatic duct appears normal along its entire course with no occlusion or dilation

impaired hearing
- ear dysfunction centered between 25 and 30 days of age
- ABR assessment shows that at 21 days of age most hemizygotes have mild to moderate unilateral hearing loss, by 25 days of age the majority have bilateral hearing loss exceeding that of controls by 30 dB, and hearing loss is progressive with onset of inner ear dysfunction centered between 25 and 30 days of age

increased or absent threshold for auditory brainstem response
- mean auditory brainstem response thresholds are also significantly higher than other Phex male mutants (Phex^Hyp, Phex^Hyp-2J, Gy)
- mean auditory brainstem response thresholds are significantly higher than controls
- this difference from other Phex mutants but not from wild-type controls disappeared when Phex^Hyp-Duk was outcrossed to BALB/cByJ

increased susceptibility to otitis media

organ of Corti degeneration
- degeneration is obvious in the apical turn of the cochlea but decreases towards the base

unilateral deafness

behavior/neurological phenotype

abnormal gait
- in some hemizygotes

circling
- 11 out of 20 males showed circling behaviour

head bobbing
- in some hemizygotes

homeostasis/metabolism phenotype

decreased circulating calcium level
- at 6 weeks of age serum Ca²⁺ are significantly decreased compared to controls

decreased circulating potassium level
- at 6 weeks of age serum PO₄ levels are significantly lower than controls

immune system phenotype

ear inflammation
- by 40 days of age most hemizygotes have severe endolymphatic hydrops with distension of Reissner's membrane
- by 90 days of age severe hydrops in all parts of the labyrinth is found and Reissner's membrane is displaced
- some hemizygotes show mild apical hydrops at 21 to 25 days of age, but this is not accompanied by hair cell loss and the endolymphatic duct appears normal along its entire course with no occlusion or dilation

increased susceptibility to otitis media

limbs/digits/tail phenotype

abnormal hindlimb morphology
- shortened hind limbs are seen

abnormal limb bone morphology

abnormal patella morphology
- growth plates of the knee are thickened and irregular

short femur

short fibula
- the fibula is shortened and splayed

short tail

short tibia
- the tibia is shortened and splayed

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - at 40 days of age the cells of the spiral ganglion and the organ of Corti remain intact

nervous system phenotype

cochlear ganglion degeneration
- at 90 days of age spiral ganglion degeneration in most turns of the cochlea is found, although the hair cells are largely preserved
- degeneration is obvious in the apical turn of the cochlea but decreases towards the base

skeleton phenotype

abnormal craniofacial bone morphology

abnormal limb bone morphology

abnormal patella morphology
- growth plates of the knee are thickened and irregular

abnormal temporal bone morphology
- the temporal bone surrounding the cochlea is thickened with areas of non-mineralization

decreased bone mineral density
- between 6 and 40 weeks of age under-mineralized bone is present throughout the body

decreased length of long bones
- the long bones are shortened

disorganized long bone epiphyseal plate
- disorganized femoral growth plates

increased diameter of long bones
- the long bones are thickened

short femur

short fibula
- the fibula is shortened and splayed

short maxilla
- the length of the upper jaw is reduced

short tibia
- the tibia is shortened and splayed

small cranium
- at 12 weeks the skull is significantly shorter in length with a shorter nose length and lower areal bone mineral density compared to controls
- skull width and skull to nose length ratio are unaffected

craniofacial phenotype

abnormal craniofacial bone morphology

abnormal temporal bone morphology
- the temporal bone surrounding the cochlea is thickened with areas of non-mineralization

short maxilla
- the length of the upper jaw is reduced

small cranium
- at 12 weeks the skull is significantly shorter in length with a shorter nose length and lower areal bone mineral density compared to controls
- skull width and skull to nose length ratio are unaffected

Genotype: Phex^Hyp-Duk/Phex⁺
involves: BALB/cAnBomUrd

behavior/neurological phenotype

circling
- some but not all females showed circling behavior

growth/size/body region phenotype

postnatal growth retardation
- some but not all females are mildly growth retarded in overall body size with a squared trunk
- unlike Phex^Hyp-2J it is not easy to distinguish between heterozygous females and wild-type females

limbs/digits/tail phenotype

abnormal hindlimb morphology
- some but not all females have shortened hind limbs

short tail
- some but not all females have a shortened tail

References

Lorenz-Depiereux B; Guido VE; Johnson KR; Zheng QY; Gagnon LH; Bauschatz JD; Davisson MT; Washburn LL; Donahue LR; Strom TM; Eicher EM. 2004. New intragenic deletions in the Phex gene clarify X-linked hypophosphatemia-related abnormalities in mice. Mamm Genome 15(3):151-61PubMed: 15029877 MGI: J:88352

Additional - Phex^Hyp-Duk related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- QPCR:Phex-Alternate 1
- Genotyping resources and troubleshooting
Appearance
- albino, small, shortened hindlimbs and tail, possible circling
  Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Phex^Hyp-Duk/Y male
  
  albino, may exhibit small size, shortened hindlimbs and tail, circling
  Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c Phex^Hyp-Duk/+ female
  
  albino, unaffected
  Related Genotype: A/A Tyrp1^b/Tyrp1^b Tyr^c/Tyr^c +/+ or +/Y
Citation
When using the hypophosphatemia Duke mouse strain in a publication, please cite the originating article(s) and include JAX stock #003905 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 wildtype for Phex<Hyp-Duk>

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Also Known As:hypophosphatemia Duke

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

PhexHyp-Duk

Allele Symbol: PhexHyp-Duk

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: PhexHyp-Duk/YB6.C-Phex/J

craniofacial phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

skeleton phenotype

Genotype: PhexHyp-Duk/Yinvolves: BALB/cAnBomUrd

adipose tissue phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

limbs/digits/tail phenotype

mammalian phenotype

nervous system phenotype

skeleton phenotype

craniofacial phenotype

Genotype: PhexHyp-Duk/Phex+involves: BALB/cAnBomUrd

behavior/neurological phenotype

growth/size/body region phenotype

limbs/digits/tail phenotype

References

Additional - PhexHyp-Duk 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

Phex^Hyp-Duk

Allele Symbol: Phex^Hyp-Duk

Genotype: Phex^Hyp-Duk/Y
B6.C-Phex/J

Genotype: Phex^Hyp-Duk/Y
involves: BALB/cAnBomUrd

Genotype: Phex^Hyp-Duk/Phex⁺
involves: BALB/cAnBomUrd

Additional - Phex^Hyp-Duk related