Generation of Genetically Modified Rats Using CRISPR/Cas9 Genome-Editing System to Reveal Novel Vitamin D Actions

January 2021 in “ Medical Research Archives ”

Miyu Nishikawa, Kaori Yasuda, Hiroki Mano, Shinichi Ikushiro, Toshiyuki Sakaki

CRISPR/Cas9 vitamin D 25-hydroxyvitamin D3 vitamin D receptor Cyp27b1-knockout Vdr-KO Vdr (R270L) rickets alopecia CRISPR 25(OH)D3 VDR

TLDR Genetically modified rats help reveal how vitamin D affects bone and skin health.

The study utilized genetically modified rats to explore the molecular mechanisms of vitamin D action, focusing on the roles of 25-hydroxyvitamin D3 (25(OH)D3) and the vitamin D receptor (VDR). Researchers generated Cyp27b1-knockout (KO), Vdr-KO, and Vdr (R270L) rats, which exhibited symptoms of rickets, such as growth retardation and abnormal bone formation. Notably, Vdr-KO rats also showed abnormal skin formation and alopecia. Administration of 25(OH)D3 alleviated rickets symptoms in Cyp27b1-KO and Vdr (R270L) rats, indicating a direct action of 25(OH)D3 via VDR-genomic pathways. The study concluded that this novel in vivo system is valuable for understanding vitamin D's molecular mechanisms.

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