Mouse Genome Informatics
ht1
     PhexHyp-Duk/Phex+
involves: BALB/cAnBomUrd
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
behavior/neurological
circling ( J:88352 )
• some but not all females showed circling behavior (J:88352)

growth/size
postnatal growth retardation ( J:88352 )
• some but not all females are mildly growth retarded in overall body size with a squared trunk (J:88352)
• unlike PhexHyp-2J it is not easy to distinguish between heterozygous females and wild-type females (J:88352)

limbs/digits/tail
abnormal hindlimb morphology ( J:88352 )
• some but not all females have shortened hind limbs (J:88352)
short tail ( J:88352 )
• some but not all females have a shortened tail (J:88352)

Mouse Models of Human Disease
 OMIM IDRef(s)
Hypophosphatemic Rickets, X-Linked Dominant; XLHR 307800 J:88352


Mouse Genome Informatics
ot2
     PhexHyp-Duk/Y
B6.C-PhexHyp-Duk/J
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype

PhexHyp-Duk/Y with littermate +/Y control

behavior/neurological
behavior/neurological phenotype ( J:132678 )
N
• Background Sensitivity: startle response is normal and no head-bobbing or circling are seen (J:132678)

growth/size

craniofacial
abnormal cranium morphology ( J:132678 )
• slightly abnormal shape (J:132678)

skeleton
abnormal cranium morphology ( J:132678 )
• slightly abnormal shape (J:132678)

hearing/vestibular/ear
hearing/vestibular/ear phenotype ( J:132678 )
N
• Background Sensitivity: startle response is normal and no head-bobbing or circling are seen (J:132678)
• 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 (J:132678)
abnormal otic capsule morphology ( 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 (J:132678)
increased or absent threshold for auditory brainstem response ( J:132678 )
• 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 (J:132678)


Mouse Genome Informatics
ot3
     PhexHyp-Duk/Y
involves: BALB/cAnBomUrd
Key:
♀ phenotype observed in females WTSI Wellcome Trust Sanger Institute
♂ phenotype observed in males Euro Europhenome
N normal phenotype
adipose tissue
decreased total body fat amount ( J:88352 )
• a significant increase in lean body mass is seen compared to controls (J:88352)

behavior/neurological
abnormal gait ( J:132678 )
• in some hemizygotes (J:132678)
head bobbing ( J:132678 )
• in some hemizygotes (J:132678)
circling ( J:88352 )
• 11 out of 20 males showed circling behaviour (J:88352)

craniofacial
small cranium ( 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 (J:88352)
• skull width and skull to nose length ratio are unaffected (J:88352)
abnormal temporal bone morphology ( J:88352 )
• the temporal bone surrounding the cochlea is thickened with areas of non-mineralization (J:88352)
short maxilla ( J:88352 )
• the length of the upper jaw is reduced (J:88352)

growth/size
decreased body weight ( J:88352 )
• all males have significantly lower body weights, ~25% less than controls (J:88352)
postnatal growth retardation ( J:88352 )
• all males are mildly growth retarded in overall body size with a squared trunk (J:88352)

hearing/vestibular/ear
hearing/vestibular/ear phenotype ( J:132678 )
N
• at 40 days of age the cells of the spiral ganglion and the organ of Corti remain intact (J:132678)
abnormal cochlea morphology ( 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 (J:88352)
organ of Corti degeneration ( J:88352 )
• degeneration is obvious in the apical turn of the cochlea but decreases towards the base (J:88352)
abnormal scala tympani morphology ( J:88352 )
• a precipitate is found in the scala tympani of the cochlea (J:88352)
abnormal vestibular saccule morphology ( J:132678 )
• in some instances at 90 days of age the saccule is ruptured apparently due to hydrops (J:132678)
abnormal otic capsule morphology ( J:132678 )
• the otic bony capsule of hemizygotes is thickened and surrounded by non-mineralized bone at around 25 days of age (J:132678)
increased or absent threshold for auditory brainstem response ( J:88352 , J:132678 )
• mean auditory brainstem response thresholds are significantly higher than controls (J:88352)
• mean auditory brainstem response thresholds are also significantly higher than other Phex male mutants (PhexHyp, PhexHyp-2J, Gy) (J:88352)
• this difference from other Phex mutants but not from wild-type controls disappeared when PhexHyp-Duk was outcrossed to BALB/cByJ (J:88352)
(J:132678)
impaired hearing ( J:132678 )
• 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 (J:132678)
ear inflammation ( 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 (J:132678)
• by 40 days of age most hemizygotes have severe endolymphatic hydrops with distension of Reissner's membrane (J:132678)
• by 90 days of age severe hydrops in all parts of the labyrinth is found and Reissner's membrane is displaced (J:132678)

homeostasis/metabolism
decreased circulating calcium level ( J:88352 )
• at 6 weeks of age serum Ca2+ are significantly decreased compared to controls (J:88352)
decreased circulating potassium level ( J:88352 )
• at 6 weeks of age serum PO4 levels are significantly lower than controls (J:88352)

limbs/digits/tail
abnormal hindlimb morphology ( J:88352 )
• shortened hind limbs are seen (J:88352)
short femur ( J:88352 )
(J:88352)
short fibula ( J:88352 )
• the fibula is shortened and splayed (J:88352)
short tibia ( J:88352 )
• the tibia is shortened and splayed (J:88352)
abnormal patella morphology ( J:88352 )
• growth plates of the knee are thickened and irregular (J:88352)
short tail ( J:88352 )
(J:88352)

skeleton
small cranium ( 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 (J:88352)
• skull width and skull to nose length ratio are unaffected (J:88352)
abnormal temporal bone morphology ( J:88352 )
• the temporal bone surrounding the cochlea is thickened with areas of non-mineralization (J:88352)
short maxilla ( J:88352 )
• the length of the upper jaw is reduced (J:88352)
short femur ( J:88352 )
(J:88352)
short fibula ( J:88352 )
• the fibula is shortened and splayed (J:88352)
short tibia ( J:88352 )
• the tibia is shortened and splayed (J:88352)
abnormal patella morphology ( J:88352 )
• growth plates of the knee are thickened and irregular (J:88352)
disorganized long bone epiphyseal plate ( J:88352 )
• disorganized femoral growth plates (J:88352)
decreased length of long bones ( J:88352 )
• the long bones are shortened (J:88352)
increased diameter of long bones ( J:88352 )
• the long bones are thickened (J:88352)
decreased bone mineral density ( J:88352 )
• between 6 and 40 weeks of age under-mineralized bone is present throughout the body (J:88352)

nervous system
cochlear ganglion degeneration ( J:88352 , J:132678 )
• degeneration is obvious in the apical turn of the cochlea but decreases towards the base (J:88352)
• at 90 days of age spiral ganglion degeneration in most turns of the cochlea is found, although the hair cells are largely preserved (J:132678)

immune system
ear inflammation ( 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 (J:132678)
• by 40 days of age most hemizygotes have severe endolymphatic hydrops with distension of Reissner's membrane (J:132678)
• by 90 days of age severe hydrops in all parts of the labyrinth is found and Reissner's membrane is displaced (J:132678)