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.
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. In 2006 sperm was cryopreserved from hemizygous males at generation F64+21. Cryo-recovery is anticipated to involve BALB/cByJ females making the cryo-recovered mice genetically distinct from the source of the cryoperserved sperm, stock #003905.
|Allele Name||hypophosphatemia, Duke|
|Gene Symbol and Name||Phex, phosphate regulating endopeptidase homolog, X-linked|
|Strain of Origin||CAnBomUrd.Cg-Foxn1nu|
|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.|