Targeted inactivation of the 25-hydroxyvitamin D(3)-1(alpha)-hydroxylase gene (CYP27B1) creates an animal model of pseudovitamin D-deficiency rickets

Endocrinology. 2001 Jul;142(7):3135-41. doi: 10.1210/endo.142.7.8281.


Pseudovitamin D-deficiency rickets is caused by mutations in the cytochrome P450 enzyme, 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase). Patients with the disease exhibit growth retardation, rickets, and osteomalacia. Serum biochemistry is characterized by hypocalcemia, secondary hyperparathyroidism, and undetectable levels of 1alpha,25-dihydroxyvitamin D(3). We have inactivated the 1alpha-OHase gene in mice after homologous recombination in embryonic stem cells. Serum analysis of homozygous mutant animals confirmed that they were hypocalcemic, hypophosphatemic, hyperparathyroidic, and that they had undetectable 1alpha,25-dihydroxyvitamin D(3). Histological analysis of the bones from 3-week-old mutant animals confirmed the evidence of rickets. At the age of 8 weeks, femurs from 1alpha-OHase-ablated mice present a severe disorganization in the architecture of the growth plate and marked osteomalacia. These results show that we have successfully inactivated the 1alpha-OHase gene in mice and established a valid animal model of pseudovitamin D-deficiency rickets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics*
  • Animals
  • Disease Models, Animal
  • Femur / pathology
  • Gene Expression / physiology
  • Gene Silencing / physiology*
  • Gene Targeting*
  • Hyperparathyroidism / etiology
  • Hypocalcemia / etiology
  • Hypophosphatemia / etiology
  • Mice
  • Mice, Inbred C57BL
  • Rickets / etiology*
  • Rickets / pathology
  • Vitamin D / physiology
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / genetics*


  • Vitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase