Phenotypes Associated with This Genotype

Genotype
MGI:3029314

• Allelic Composition: Slc34a1^tm1Hten/Slc34a1^tm1Hten
• Genetic Background: involves: 129S2/SvPas * C57BL/6J

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Histological appearance of bone from wild-type, Slc34a1^tm1Hten/Slc34a1⁺ and Slc34a1^tm1Hten/Slc34a1^tm1Hten mice

mortality/aging

postnatal lethality ( J:47637 )

• 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

lethargy ( J:47637 )

• homozygotes display some lethargy during the first 2 weeks of life

abnormal eating behavior ( J:47637 )

• homozygotes frequently have difficulties in feeding during the first 2 weeks of life

growth/size/body

decreased birth body size ( J:47637 )

• at birth, homozygotes are noticeably smaller than wild-type littermates

decreased birth weight ( J:47637 )

• 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)

decreased body size ( J:47637 )

• homozygotes remain significantly smaller than wild-type littermates for at least 4 months after birth

decreased body weight ( J:47637 )

• homozygotes maintain a significantly lower body weight for at least 4 months after birth

homeostasis/metabolism

decreased circulating parathyroid hormone level ( J:47637 )

• at 2-3 months of age, serum PTH levels are appropriately decreased in response to hypercalciuria

increased circulating calcium level ( J:47637 )

• serum calcium levels are slightly but significantly increased at all ages examined, in an age-independent manner

decreased circulating phosphate level ( J:47637 )

• at 1-7 months of age, serum inorganic phosphate (Pi) levels are significantly reduced

increased circulating alkaline phosphatase level ( J:47637 )

• 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

abnormal vitamin D level ( J:47637 )

• at 1-3 months of age, homozygotes exhibit an appropriate adaptive increase in serum 1,25(OH)₂D levels in response to hypophosphatemia

increased urine calcium level ( J:47637 )

• at 1 month of age, the urine calcium/creatinine ratio and the fractional excretion index for calcium (FEI_Ca) are significantly increased

increased urine phosphate level ( J:47637 )

• at 1 month of age, the urine Pi/creatinine ratio and the fractional excretion index for Pi (FEI_Pi) are strikingly increased

renal/urinary system

renal/urinary system phenotype ( J:47637 )

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

increased urine calcium level ( J:47637 )

• at 1 month of age, the urine calcium/creatinine ratio and the fractional excretion index for calcium (FEI_Ca) are significantly increased

increased urine phosphate level ( J:47637 )

• at 1 month of age, the urine Pi/creatinine ratio and the fractional excretion index for Pi (FEI_Pi) are strikingly increased

skeleton

skeleton phenotype ( J:47637 )

N • homozygotes do not exhibit rickets or osteomalacia

abnormal trabecular bone morphology ( J:47637 )

• poor initial development of cancellous bone

• by 45 days of age, the number metaphyseal trabeculae exceeded that in wild-type

abnormal skeleton development ( J:47637 )

• 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

delayed bone ossification ( J:47637 )

muscle

muscle weakness ( J:47637 )

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

reproductive system

reduced fertility ( J:47637 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary hypophosphatemic rickets with hypercalciuria		DOID:0050947	OMIM:241530	J:47637