Journal Article

Targeted ablation of the vitamin D receptor: an animal model of vitamin D-dependent rickets type II with alopecia

Pirro, A.E, Amling, M, Baron, R, Demay, M.B, Delling, G, Li, Y.C, Bronson, R

1997

Overview

Vitamin D, the major steroid hormone that controls mineral ion homeostasis, exerts its actions through the vitamin D receptor (VDR). The VDR is expressed in many tissues, including several tissues not thought to play a role in mineral metabolism. Studies in kindreds with VDR mutations (vitamin D-dependent rickets type II, VDDR II) have demonstrated hypocalcemia, hyperparathyroidism, rickets, and osteomalacia. Alopecia, which is not a feature of vitamin D deficiency, is seen in some kindreds. We have generated a mouse model of VDDR II by targeted ablation of the second zinc finger of the VDR DNA-binding domain. Despite known expression of the VDR in fetal life, homozygous mice are phenotypically normal at birth and demonstrate normal survival at least until 6 months. They become hypocalcemic at 21 days of age, at which time their parathyroid hormone (PTH) levels begin to rise. Hyperparathyroidism is accompanied by an increase in the size of the parathyroid gland as well as an increase in PTH mRNA levels. Rickets and osteomalacia are seen by day 35; however, as early as day 15, there is an expansion in the zone of hypertrophic chondrocytes in the growth plate. In contrast to animals made vitamin D deficient by dietary means, and like some patients with VDDR II, these mice develop progressive alopecia from the age of 4 weeks.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,The National Academy of Sciences of the USA
• Subject: ADN / Alopecia / ANIMAL MODELS / Animals / BINDING PROTEINS / Biological Sciences / Cell lines / DELETIONS / Developmental biology / Disease Models, Animal / DNA / DNA BINDING MOTIFS / DNA-binding domains / DNA-binding proteins / ENDOCRINE DISEASES / ENFERMEDADES DE LA PIEL / ENFERMEDADES GLANDULAS ENDOCRINAS / Epiphyses / Exons / EXPERIMENTACION IN VIVO / EXPERIMENTATION IN VIVO / Gene Targeting / genetics / GLANDULA PARATIROIDE / HIPOCALCEMIA / HOMOLOGOUS RECOMBINATION / HYPERPARATHYROIDISM / HYPOCALCAEMIA / HYPOCALCEMIA / HYPOCALCEMIE / IN VIVO EXPERIMENTATION / INDUCED MUTATION / MALADIE DE LA PEAU / MICE / MODELE ANIMAL / MODELOS ANIMALES / MUTACION INDUCIDA / mutagenesis / MUTATION PROVOQUEE / OSTEODISTROFIA / OSTEODYSTROPHIE / OSTEODYSTROPHY / OSTEOMALACIA / PARATHYROID GLAND / PARATHYROIDE / PROTEINAS AGLUTINANTES / PROTEINE DE LIAISON / RACHITISME / RAQUITISMO / RATON / Receptors / Receptors, Calcitriol / Receptors, Calcitriol - genetics / RECOMBINACION / RECOMBINAISON / RECOMBINATION / RICKETS / SKIN DISEASES / SOURIS / Transfection / TROUBLE ENDOCRINIEN / VITAMIN D / Vitamin D Deficiency / VITAMINA D / VITAMINE D / Zinc Fingers / Zinc Fingers - genetics