Strain Name:

BALB/cAnBomUrd-PhexHyp-Duk/J

Stock Number:

003905

Availability:

Under Development for Cryopreservation Repository

To register your interest in this strain go to the Strain Interest Form.

Description

Strain Information

Former Names BALB/cAnBomUrd-PhexUrd    (Changed: 15-DEC-04 )
Type Coisogenic; Mutant Strain; Spontaneous Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationF64+20+F7 (06-DEC-07)

Appearance
albino, small, shortened hindlimbs and tail, possible circling
Related Genotype: A/A Tyrp1b/Tyrp1b Tyrc/Tyrc PhexHyp-Duk/Y male

albino, may exhibit small size, shortened hindlimbs and tail, circling
Related Genotype: A/A Tyrp1b/Tyrp1b Tyrc/Tyrc PhexHyp-Duk/+ female

albino, unaffected
Related Genotype: A/A Tyrp1b/Tyrp1b Tyrc/Tyrc +/+ or +/Y

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 Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   PhexHyp-Duk allele
005068   B6.C-PhexHyp-Duk/J
005852   BALB/c-PhexHyp-Duk/J
View Strains carrying   PhexHyp-Duk     (2 strains)

Strains carrying other alleles of Phex
000528   B6.Cg-PhexHyp/J
003950   C57BL/6-PhexHyp-2J/J
View Strains carrying other alleles of Phex     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms
Hypophosphatemic Rickets, X-Linked Dominant - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

PhexHyp-Duk/Phex+

        involves: BALB/cAnBomUrd
  • behavior/neurological phenotype
  • circling (MGI Ref ID J:88352)
    • some but not all females showed circling behavior
  • growth/size phenotype
  • postnatal growth retardation (MGI Ref ID J:88352)
    • some but not all females are mildly growth retarded in overall body size with a squared trunk
    • unlike PhexHyp-2J it is not easy to distinguish between heterozygous females and wild-type females
  • limbs/digits/tail phenotype
  • abnormal hindlimb morphology (MGI Ref ID J:88352)
    • some but not all females have shortened hind limbs
  • short tail (MGI Ref ID J:88352)
    • some but not all females have a shortened tail
  • hearing/vestibular/ear phenotype
  • circling (MGI Ref ID J:88352)
    • some but not all females showed circling behavior

PhexHyp-Duk/Y

        involves: BALB/cAnBomUrd
  • adipose tissue phenotype
  • decreased adipose tissue amount (MGI Ref ID J:88352)
    • a significant increase in lean body mass is seen compared to controls
  • behavior/neurological phenotype
  • abnormal gait (MGI Ref ID J:132678)
    • in some hemizygotes
  • circling (MGI Ref ID J:88352)
    • 11 out of 20 males showed circling behaviour
  • head bobbing (MGI Ref ID J:132678)
    • in some hemizygotes
  • craniofacial phenotype
  • abnormal craniofacial bone morphology (MGI Ref ID J:88352)
    • abnormal temporal bone morphology (MGI Ref ID J:88352)
      • the temporal bone surrounding the cochlea is thickened with areas of non-mineralization
    • short maxilla (MGI Ref ID J:88352)
      • the length of the upper jaw is reduced
    • small skull (MGI Ref ID J:88352)
      • 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
  • growth/size phenotype
  • decreased body weight (MGI Ref ID J:88352)
    • all males have significantly lower body weights, ~25% less than controls
  • postnatal growth retardation (MGI Ref ID J:88352)
    • all males are mildly growth retarded in overall body size with a squared trunk
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:132678)
    • at 40 days of age the cells of the spiral ganglion and the organ of Corti remain intact
    • abnormal inner ear morphology (MGI Ref ID J:88352)
      • abnormal cochlea morphology (MGI Ref ID J:88352)
        • 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 scala tympani morphology (MGI Ref ID J:88352)
          • a precipitate is found in the scala tympani of the cochlea
        • distended Reissner membrane (MGI Ref ID J:132678)
        • organ of Corti degeneration (MGI Ref ID J:88352)
          • degeneration is obvious in the apical turn of the cochlea but decreases towards the base
      • abnormal otic capsule morphology (MGI Ref ID J:132678)
        • the otic bony capsule of hemizygotes is thickened and surrounded by non-mineralized bone at around 25 days of age
      • abnormal saccule morphology (MGI Ref ID J:132678)
        • in some instances at 90 days of age the saccule is ruptured apparently due to hydrops
    • circling (MGI Ref ID J:88352)
      • 11 out of 20 males showed circling behaviour
    • decreased brainstem auditory evoked potential (MGI Ref ID J:88352)
      • mean auditory brainstem response thresholds are significantly higher than controls
      • mean auditory brainstem response thresholds are also significantly higher than other Phex male mutants (PhexHyp, PhexHyp-2J, Gy)
      • this difference from other Phex mutants but not from wild-type controls disappeared when PhexHyp-Duk was outcrossed to BALB/cByJ
      • 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
    • ear inflammation (MGI Ref ID J:132678)
      • 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
      • 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
      • increased susceptibility to otitis media (MGI Ref ID J:132678)
    • head bobbing (MGI Ref ID J:132678)
      • in some hemizygotes
    • unilateral deafness (MGI Ref ID J:132678)
  • homeostasis/metabolism phenotype
  • decreased circulating potassium level (MGI Ref ID J:88352)
    • at 6 weeks of age serum PO4 levels are significantly lower than controls
  • hypocalcemia (MGI Ref ID J:88352)
    • at 6 weeks of age serum Ca2+ are significantly decreased compared to controls
  • limbs/digits/tail phenotype
  • abnormal hindlimb morphology (MGI Ref ID J:88352)
    • shortened hind limbs are seen
  • abnormal skeleton extremities morphology (MGI Ref ID J:88352)
    • abnormal patella morphology (MGI Ref ID J:88352)
      • growth plates of the knee are thickened and irregular
    • decreased length of long bones (MGI Ref ID J:88352)
      • the long bones are shortened
      • short femur (MGI Ref ID J:88352)
      • short fibula (MGI Ref ID J:88352)
        • the fibula is shortened and splayed
      • short tibia (MGI Ref ID J:88352)
        • the tibia is shortened and splayed
    • increased diameter of long bones (MGI Ref ID J:88352)
      • the long bones are thickened
  • short tail (MGI Ref ID J:88352)
  • skeleton phenotype
  • abnormal craniofacial bone morphology (MGI Ref ID J:88352)
    • abnormal temporal bone morphology (MGI Ref ID J:88352)
      • the temporal bone surrounding the cochlea is thickened with areas of non-mineralization
    • short maxilla (MGI Ref ID J:88352)
      • the length of the upper jaw is reduced
    • small skull (MGI Ref ID J:88352)
      • 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
  • abnormal skeleton extremities morphology (MGI Ref ID J:88352)
    • abnormal patella morphology (MGI Ref ID J:88352)
      • growth plates of the knee are thickened and irregular
    • decreased length of long bones (MGI Ref ID J:88352)
      • the long bones are shortened
      • short femur (MGI Ref ID J:88352)
      • short fibula (MGI Ref ID J:88352)
        • the fibula is shortened and splayed
      • short tibia (MGI Ref ID J:88352)
        • the tibia is shortened and splayed
    • increased diameter of long bones (MGI Ref ID J:88352)
      • the long bones are thickened
  • decreased bone density (MGI Ref ID J:88352)
    • between 6 and 40 weeks of age under-mineralized bone is present throughout the body
  • disorganized long bone epiphyseal plate (MGI Ref ID J:88352)
    • disorganized femoral growth plates
  • nervous system phenotype
  • cochlear ganglion degeneration (MGI Ref ID J:88352)
    • degeneration is obvious in the apical turn of the cochlea but decreases towards the base
    • at 90 days of age spiral ganglion degeneration in most turns of the cochlea is found, although the hair cells are largely preserved
  • immune system phenotype
  • ear inflammation (MGI Ref ID J:132678)
    • 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
    • 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
    • increased susceptibility to otitis media (MGI Ref ID J:132678)

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

PhexHyp-Duk/Y

        B6.C-PhexHyp-Duk/J
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype (MGI Ref ID J:132678)
    • startle response is normal and no head-bobbing or circling are seen
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:132678)
  • craniofacial phenotype
  • abnormal skull morphology (MGI Ref ID J:132678)
    • slightly abnormal shape
  • skeleton phenotype
  • abnormal skull morphology (MGI Ref ID J:132678)
    • slightly abnormal shape
  • hearing/vestibular/ear phenotype
  • *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:132678)
    • startle response is normal and no head-bobbing or circling are seen
    • 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
    • abnormal otic capsule morphology (MGI Ref ID J:132678)
      • 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
    • decreased brainstem auditory evoked potential (MGI Ref ID J:132678)
      • 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

Genes & Alleles

Gene & Allele Information

Allele Symbol PhexHyp-Duk
Allele Name hypophosphatemia, Duke
Allele Type Spontaneous
Strain of OriginCAnBomUrd.Cg-Foxn1
Gene Symbol and Name Phex, phosphate regulating gene with homologies to endopeptidases on the X chromosome (hypophosphatemia, vitamin D resistant rickets)
Chromosome X
Gene Common Name(s) Gy; HPDR; HPDR1; HYP; HYP1; Hyp; PEX; XLH; gyro; hypophosphatemia;
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.

Genotyping

Genotyping Information

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

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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):151-61. [PubMed: 15029877]  [MGI Ref ID J:88352]

Additional References

PhexHyp-Duk related

Megerian CA; Semaan MT; Aftab S; Kisley LB; Zheng QY; Pawlowski KS; Wright CG; Alagramam KN. 2008. A mouse model with postnatal endolymphatic hydrops and hearing loss. Hear Res 237(1-2):90-105. [PubMed: 18289812]  [MGI Ref ID J:132678]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

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

 

This strain is currently Under Development for Cryopreservation Repository.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

View All Strains Under Development and On Hold

Supply Details

Standard SupplyUnder Development for Cryopreservation Repository
Supply Notes

Control Information

  Control
   Wild-type 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.

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