Hypophosphatemia (Phex^Hyp) is an X-linked semidominant mutation that causes defects in phosphate metabolism. It is allelic with the gyro mutation (Phex^Gy) but hypophosphatemia mutant mice do not circle. Hemizygous males and heterozygous females can be recognized at 20 to 30 days of age by their shortened hindlimbs and tail. They have reduced body size which persists throughout life, and skeletal changes resembling rickets. Hemizygous males are more affected than heterozygous females. Viability is normal in both sexes, but heterozygous females show better fertility than hemizygous males.

Development

Initially misnamed osteopetrotic (Op), the hypophosphatemia mutation arose spontaneously in 1968 in a C57BL/6J stock bearing the quaking mutation. The quaking mutation arose in the DBA/2J strain in 1961, and was crossed twice to the C3H strain before being crossed onto C57BL/6J. The hypophosphatemia mutation has been maintained by backcrossing heterozygous females to C57BL/6J males. In 1984 this strain reached generation N20 and in 2008 it reached generation N100.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Genetics

Phex^Hyp

Allele Symbol: Phex^Hyp

Allele Name	hypophosphatemia
Allele Type	Spontaneous (Not Specified)
Allele Synonym(s)	Hyp; Op
Gene Symbol and Name	Phex, phosphate regulating endopeptidase homolog, X-linked
Gene Synonym(s)
Strain of Origin	B6.Cg-Qk^qk-v
Chromosome	X
Molecular Note	The mutation in the Hyp mouse is a deletion that includes exons 16-22 of the 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

Research Areas By Phenotype

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

Genotype: Phex^Hyp related

Endocrine Deficiency Research
- Bone/Bone Marrow Defects
- Gastrointestinal Defects
- Kidney Defects
Internal/Organ Research
- Gastrointestinal Defects
- Kidney Defects
- Skeleton
  - Bone
Mouse/Human Gene Homologs
- hypophosphatemic D-resistant rickets, X-linked
Developmental Biology Research
- Skeletal Defects
Sensorineural Research
- Hearing Defects
  - hypophosphatemic rickets X-linked

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/Y
Not Specified

growth/size/body region phenotype

decreased body length
- evident at 2 weeks of age

decreased body weight
- evident at 2 weeks of age

skeleton phenotype

abnormal osteocyte lacuna morphology
- osteocyte lacunae are increased in size and randomly organized compared to those in control bone

rickets
- male mice show age dependent growth retardation and skeletal dysplasia as a consequence of rickets

decreased length of long bones

abnormal bone mineralization
- male mice display osteoidosis and impaired mineralization

abnormal osteocyte lacunocanalicular system morphology
- the inner lacunocanalicular wall is buckled and enlarged

decreased bone mineral density
- there is about a 54% decrease in bone mineral density

osteomalacia
- osteomalacia characterized by hyperosteoidosis and an excess of unmineralilized osteoid

abnormal long bone hypertrophic chondrocyte zone
- an increase in this zone is evident

short femur

homeostasis/metabolism phenotype

decreased circulating phosphate level
- at 8 weeks of age
- serum levels are decreased by ~40% compared to wild-type at 6 weeks

abnormal renal phosphate reabsorption
- reduction in renal phosphate uptake at 8 weeks of age

abnormal vitamin D level
- male mice show a 63% decrease in serum 1,25(OH)₂D₃ concentrations compared to wild-type at 6 weeks

limbs/digits/tail phenotype

short femur

renal/urinary system phenotype

abnormal renal phosphate reabsorption
- reduction in renal phosphate uptake at 8 weeks of age

Genotype: Phex^Hyp/Phex^Hyp
involves: C3H/HeSnJ * C57BL/6J

digestive/alimentary phenotype

abnormal intestinal absorption

homeostasis/metabolism phenotype

decreased circulating phosphate level

Genotype: Phex^Hyp/Y
involves: C3H/HeSnJ * C57BL/6J

digestive/alimentary phenotype

abnormal intestinal absorption

homeostasis/metabolism phenotype

decreased circulating phosphate level

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

Genotype: Phex^Hyp/Phex^Hyp
B6.Cg-Phex/J

cellular phenotype

maternal effect
- heterozygous offspring from homozygous females have shorter caudal vertebrae and increased osteoid within cancellous bone than do heterozygotes derived from hemizygous males

homeostasis/metabolism phenotype

decreased circulating phosphate level
- serum phosphate is significantly reduced relative to wild-type but similarity in serum phosphate levels between heterozygotes, homozygotes and hemizygotes indicates that there is not a gene dose effect

limbs/digits/tail phenotype

small caudal vertebrae

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

skeleton phenotype

osteomalacia
- there is a significant increase in cancellous osteoid volume per bone volume, and cancellous, endocortical, and periosteal osteoid thickness

small caudal vertebrae

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

Genotype: Phex^Hyp/?
involves: C57BL/6J

homeostasis/metabolism phenotype

decreased circulating phosphate level
- serum phosphate levels are normal at E18.5 but by 10 days of age, significant hypophosphatemia is observed

skeleton phenotype

abnormal chondrocyte physiology
- significant decrease in hypertrophic chondrocyte apoptosis compared to controls

enthesitis
- mutants exhibit mineralizing enthesopathy of the Achilles insertion (abnormal bony projection at the attachment of the tendon) as indicated by an expansion of type II collagen expressing mineralizing fibrochondrocytes in the Achilles tendon at 12 weeks of age leading to increased mineralization of the entheses
- age leading to increased mineralization of the entheses
- treatment with oral phosphate and calcitriol does not significantly alter the hyperplasia of mineralizing fibrocartilage cells in the Achilles insertion at 12 weeks of age, however it did increase serum phosphate levels and exacerbated mineralization of the matrix surrounding the lacunae of fibrocartilage
- he matrix surrounding the lacunae of fibrocartilage

increased width of hypertrophic chondrocyte zone
- growth plates are normal at E18.5, but by 10 days of age, expansion of the late hypertrophic chondrocyte layer is evident

abnormal fibrocartilage morphology
- increase in total fibrocartilage with age

rickets

Genotype: Phex^Hyp/Phex^Hyp
involves: C57BL/6J

digestive/alimentary phenotype

decreased intestinal calcium absorption
- at 4 weeks, mice exhibit reduced calcium absorption in the duodenum compared with wild-type mice

growth/size/body region phenotype

decreased body weight

homeostasis/metabolism phenotype

decreased circulating phosphate level

skeleton phenotype

abnormal cranium morphology
- mice exhibit a shorter length from mandibular foramen to third molar compared with wild-type mice
- mice exhibit smaller cranial length, neurocranial length, and length from anterior to posterior palatine foramen compared with wild-type mice

short nasal bone

short mandible

abnormal cranial suture morphology
- mice exhibit prominent bulges at the frontonasal suture and the premaxiallary-maxillary suture unlike in wild-type mice

domed cranium

short premaxilla

short frontal bone

decreased cranium height

craniofacial phenotype

abnormal cranium morphology
- mice exhibit smaller cranial length, neurocranial length, and length from anterior to posterior palatine foramen compared with wild-type mice
- mice exhibit a shorter length from mandibular foramen to third molar compared with wild-type mice

short mandible

abnormal cranial suture morphology
- mice exhibit prominent bulges at the frontonasal suture and the premaxiallary-maxillary suture unlike in wild-type mice

decreased cranium height

domed cranium

short nasal bone

short frontal bone

short premaxilla

Genotype: Phex^Hyp/Y
involves: C57BL/6J

craniofacial phenotype

abnormal cranial suture morphology
- mice exhibit prominent bulges at the frontonasal suture and the premaxiallary-maxillary suture unlike in wild-type mice

short frontal bone

short mandible

short nasal bone

abnormal cranium morphology
- mice exhibit smaller cranial length, neurocranial length, and length from anterior to posterior palatine foramen compared with wild-type mice

short premaxilla

domed cranium

decreased cranium height

growth/size/body region phenotype

decreased body weight

homeostasis/metabolism phenotype

decreased circulating phosphate level

skeleton phenotype

short mandible

abnormal cranial suture morphology
- mice exhibit prominent bulges at the frontonasal suture and the premaxiallary-maxillary suture unlike in wild-type mice

short nasal bone

short premaxilla

abnormal cranium morphology
- mice exhibit smaller cranial length, neurocranial length, and length from anterior to posterior palatine foramen compared with wild-type mice

short frontal bone

decreased cranium height

domed cranium

digestive/alimentary phenotype

decreased intestinal calcium absorption
- at 4 weeks, mice exhibit reduced calcium absorption in the duodenum compared with wild-type mice

Genotype: Phex^Hyp/Phex⁺
B6.Cg-Phex/J

digestive/alimentary phenotype

abnormal intestinal absorption
- age related malabsorption of phosphate such that at 4 weeks of age there is decreased phosphate absorption into isolated intestinal segments, particularly in the jejunum, in both hemizygous males and heterozygous females, but this malabsorption diminishes with age and approaches normal levels by 12 weeks of age

skeleton phenotype

osteomalacia
- there is a significant increase in cancellous osteoid volume per bone volume, and cancellous, endocortical, and periosteal osteoid thickness

small caudal vertebrae
- there is a gene dose effect such that the length of the proximal caudal vertebrae in heterozygotes is intermediate between that of wild-type and homozygous females, although similarly thickened growth plates are found in heterozygotes, homozygotes, and hemizygotes
- mizygotes

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

growth/size/body region phenotype

abnormal postnatal growth/weight/body size
- all females have a squared trunk

homeostasis/metabolism phenotype

decreased circulating phosphate level
- serum phosphate is significantly reduced relative to wild-type but similarity in serum phosphate levels between heterozygotes, homozygotes and hemizygotes indicates that there is not a gene dose effect

limbs/digits/tail phenotype

short tail

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

abnormal hindlimb morphology
- shortened hind limbs are seen

small caudal vertebrae
- mizygotes
- there is a gene dose effect such that the length of the proximal caudal vertebrae in heterozygotes is intermediate between that of wild-type and homozygous females, although similarly thickened growth plates are found in heterozygotes, homozygotes, and hemizygotes

mammalian phenotype

cellular phenotype
- Normal - the gamete of origin, maternal or paternal, does not impact the serum phosphate levels

Genotype: Phex^Hyp/Y
B6.Cg-Phex/J

digestive/alimentary phenotype

abnormal intestinal absorption
- with age and approaches normal levels by 12 weeks of age
- age related malabsorption of phosphate such that at 4 weeks of age there is decreased phosphate absorption into isolated intestinal segments, particularly in the jejunum, in both hemizygous males and heterozygous females, but this malabsorption diminishes with age and approaches normal levels by 12 weeks of age

skeleton phenotype

small caudal vertebrae

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

short tibia
- the tibia is shortened and splayed

short femur

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

increased diameter of long bones
- the long bones are thickened

decreased bone mineralization
- hypomineralization

short fibula
- the fibula is shortened and splayed

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

disorganized long bone epiphyseal plate
- disorganized femoral growth plates

osteomalacia
- there is a significant increase in cancellous osteoid volume per bone volume, and cancellous, endocortical, and periosteal osteoid thickness

growth/size/body region phenotype

decreased body weight
- all males have significantly lower body weights (~25% less than controls) and a squared trunk

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- mean auditory brainstem response thresholds are significantly higher than controls

homeostasis/metabolism phenotype

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

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

decreased circulating phosphate level
- serum phosphate is significantly reduced relative to wild-type but similarity in serum phosphate levels between heterozygotes, homozygotes and hemizygotes indicates that there is not a gene dose effect

limbs/digits/tail phenotype

abnormal hindlimb morphology
- shortened hind limbs are seen

short tail

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

abnormal caudal vertebrae morphology
- the overall length of the proximal caudal vertebrae is shorter, the growth plate is thicker than in wild-type controls, and there is accumulation of osteoid

short femur

short tibia
- the tibia is shortened and splayed

small caudal vertebrae

short fibula
- the fibula is shortened and splayed

Genotype: Phex^Hyp/Y
involves: C57BL/6

homeostasis/metabolism phenotype

increased circulating alkaline phosphatase level

abnormal renal glucose reabsorption
- renal D-glucose uptake is enhanced compared to in wild-type mice

decreased circulating phosphate level

increased urine phosphate level

abnormal urine nucleotide level
- urinary cAMP is increased compared to in wild-type mice

renal/urinary system phenotype

increased urine phosphate level

abnormal urine nucleotide level
- urinary cAMP is increased compared to in wild-type mice

abnormal renal glucose reabsorption
- renal D-glucose uptake is enhanced compared to in wild-type mice

References

Additional References

Argiro L; Desbarats M; Glorieux FH; Ecarot B. 2001. Mepe, the gene encoding a tumor-secreted protein in oncogenic hypophosphatemic osteomalacia, is expressed in bone. Genomics 74(3):342-51PubMed: 11414762 MGI: J:70223
Azam N; Zhang MY; Wang X; Tenenhouse HS; Portale AA. 2003. Disordered regulation of renal 25-hydroxyvitamin D-1alpha-hydroxylase gene expression by phosphorus in X-linked hypophosphatemic (hyp) mice. Endocrinology 144(8):3463-8PubMed: 12865326 MGI: J:84821
Eicher EM; Southard JL; Scriver CR; Glorieux FH. 1976. Hypophosphatemia: mouse model for human familial hypophosphatemic (vitamin D-resistant) rickets. Proc Natl Acad Sci U S A 73(12):4667-71PubMed: 188049 MGI: J:5749
Liu S; Guo R; Tu Q; Quarles LD. 2002. Overexpression of Phex in osteoblasts fails to rescue the Hyp mouse phenotype. J Biol Chem 277(5):3686-97PubMed: 11713245 MGI: J:74324
Meyer RA Jr; Gray RW; Roos BA; Kiebzak GM. 1982. Increased plasma 1,25-dihydroxyvitamin D after low calcium challenge in X-linked hypophosphatemic mice. Endocrinology 111(1):174-7PubMed: 6896304 MGI: J:6776
Strom TM; Francis F; Lorenz B; Boddrich A; Econs MJ; Lehrach H ; Meitinger T. 1997. Pex gene deletions in Gy and Hyp mice provide mouse models for X-linked hypophosphatemia. Hum Mol Genet 6(2):165-71PubMed: 9063736 MGI: J:38621

Additional - Phex^Hyp related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Phex
- Probe:Phex Probe Alternate1
- Genotyping resources and troubleshooting
Appearance
- black, reduced body size with shortened hindlimbs and tail
  Related Genotype: a/a Phex^Hyp/+
  
  black, unaffected
  Related Genotype: a/a +/?
Citation
When using the hypophosphatemia mouse strain in a publication, please cite the originating article(s) and include JAX stock #000528 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
> >	X linked - Heterozygous Females and Wildtype Males for Phex<Hyp> Minimum 2 pair

Related Products and Services

Frozen Mouse Embryo	B6.Cg-Phex<Hyp>/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Phex<Hyp>/J	$2595.00
Frozen Mouse Embryo	B6.Cg-Phex<Hyp>/J	$3373.50
Frozen Mouse Embryo	B6.Cg-Phex<Hyp>/J	$3373.50

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The Jackson Laboratory's Genotype Promise

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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Email: TechTran@jax.org

Also Known As:hypophosphatemia

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

PhexHyp

Allele Symbol: PhexHyp

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).

Research Areas By Phenotype

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

Genotype: PhexHyp related

Mammalian Phenotype Terms by Genotype

Genotype: PhexHyp/YNot Specified

growth/size/body region phenotype

skeleton phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

renal/urinary system phenotype

Genotype: PhexHyp/PhexHypinvolves: C3H/HeSnJ * C57BL/6J

digestive/alimentary phenotype

homeostasis/metabolism phenotype

Genotype: PhexHyp/Yinvolves: C3H/HeSnJ * C57BL/6J

digestive/alimentary phenotype

homeostasis/metabolism phenotype

Genotype: PhexHyp/PhexHypB6.Cg-Phex/J

cellular phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

skeleton phenotype

Genotype: PhexHyp/?involves: C57BL/6J

homeostasis/metabolism phenotype

skeleton phenotype

Genotype: PhexHyp/PhexHypinvolves: C57BL/6J

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

skeleton phenotype

craniofacial phenotype

Genotype: PhexHyp/Yinvolves: C57BL/6J

craniofacial phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

skeleton phenotype

digestive/alimentary phenotype

Genotype: PhexHyp/Phex+B6.Cg-Phex/J

digestive/alimentary phenotype

skeleton phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

mammalian phenotype

Genotype: PhexHyp/YB6.Cg-Phex/J

digestive/alimentary phenotype

skeleton phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

limbs/digits/tail phenotype

Genotype: PhexHyp/Yinvolves: C57BL/6

homeostasis/metabolism phenotype

renal/urinary system phenotype

References

Additional References

Additional - PhexHyp 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Phex^Hyp

Allele Symbol: Phex^Hyp

Genotype: Phex^Hyp related

Genotype: Phex^Hyp/Y
Not Specified

Genotype: Phex^Hyp/Phex^Hyp
involves: C3H/HeSnJ * C57BL/6J

Genotype: Phex^Hyp/Y
involves: C3H/HeSnJ * C57BL/6J

Genotype: Phex^Hyp/Phex^Hyp
B6.Cg-Phex/J

Genotype: Phex^Hyp/?
involves: C57BL/6J

Genotype: Phex^Hyp/Phex^Hyp
involves: C57BL/6J

Genotype: Phex^Hyp/Y
involves: C57BL/6J

Genotype: Phex^Hyp/Phex⁺
B6.Cg-Phex/J

Genotype: Phex^Hyp/Y
B6.Cg-Phex/J

Genotype: Phex^Hyp/Y
involves: C57BL/6

Additional - Phex^Hyp related