Mouse Genome Informatics
hm
    Slc34a1tm1Hten/Slc34a1tm1Hten
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Histological appearance of bone from wild-type, Slc34a1tm1Hten/Slc34a1+ and Slc34a1tm1Hten/Slc34a1tm1Hten mice

mortality/aging
• 44% of homozygotes die before or at weaning
• death is attributed to poor nutritional status
• homozygotes that survive weaning appear normal thereafter, despite smaller size and lower body weight

behavior/neurological
• homozygotes frequently have difficulties in feeding during the first 2 weeks of life
• homozygotes display some lethargy during the first 2 weeks of life

growth/size
• at birth, homozygotes are noticeably smaller than wild-type littermates
• at birth, homozygotes exhibit a significantly reduced body weight relative to wild-type controls (1.49 0.08 g vs 1.89 0.12 g)
• homozygotes remain significantly smaller than wild-type littermates for at least 4 months after birth
• homozygotes maintain a significantly lower body weight for at least 4 months after birth

homeostasis/metabolism
• at 2-3 months of age, serum PTH levels are appropriately decreased in response to hypercalciuria
• serum calcium levels are slightly but significantly increased at all ages examined, in an age-independent manner
• at 1-7 months of age, serum inorganic phosphate (Pi) levels are significantly reduced
• young homozygotes display significantly higher serum ALPase activity relative to age-matched wild-type and heterozygous mice
• however, by 4 months of age, serum ALPase activity is comparable in all three genotypes
• at 1-3 months of age, homozygotes exhibit an appropriate adaptive increase in serum 1,25(OH)2D levels in response to hypophosphatemia
• at 1 month of age, the urine calcium/creatinine ratio and the fractional excretion index for calcium (FEICa) are significantly increased
• at 1 month of age, the urine Pi/creatinine ratio and the fractional excretion index for Pi (FEIPi) are strikingly increased

renal/urinary system
N
• homozygotes show no evidence for amino aciduria, glycosuria, or proteinuria, indicating that the renal inorganic phosphate leak is not due to a generalized tubulopathy (J:47637)
• at 1 month of age, the urine calcium/creatinine ratio and the fractional excretion index for calcium (FEICa) are significantly increased
• at 1 month of age, the urine Pi/creatinine ratio and the fractional excretion index for Pi (FEIPi) are strikingly increased

skeleton
N
• homozygotes do not exhibit rickets or osteomalacia (J:47637)
• poor initial development of cancellous bone
• by 45 days of age, the number metaphyseal trabeculae exceeded that in wild-type
• initial impairment of secondary ossification in the epiphysis observed at 21 days of age
• by 45 days of age, the skeletal phenotype had reversed and overcompensated

muscle
• homozygotes display apparent muscle weakness during the first 2 weeks of life

reproductive system
• homozygotes display reduced reproductive ability relative to wild-type and heterozygous controls

Mouse Models of Human Disease
OMIM IDRef(s)
Hypophosphatemic Rickets with Hypercalciuria, Hereditary; HHRH 241530 J:47637