Vitamin D deficiency is well known to be associated with myopathies. Individuals with severe vitamin D deficiency develop muscle pains, cramps, and frailty. However, how vitamin D deficiency leads to myopathies was not well understood. We addressed this important problem using mice lacking vitamin D receptor.
Vitamin D functions as a steroid hormone. It binds to the Vitamin D receptor (VDR), a nuclear receptor. Ligand-bound VDR binds to DNA and regulates the transcription of target genes.
VDRKO mice are genetically modified mice in which the VDR gene is disrupted. They cannot make functional vitamin D receptor and therefore, they cannot respond to vitamin D. These mice exhibit severe growth defects, weakness, hypocalcemia, etc. They are immunocompromised and develop severe skeletal muscle atrophy. Without calcium supplementation, they die within 8 weeks.