STRA6: A gatekeeper of neuronal vitamin A homeostasis

Mutations in the STRA6 gene are associated with fatal Human Micro‐ophthalmic Syndrome 9. We generated a mouse model to elucidate the biochemical basis of this congenital disease. These mice failed to transport vitamin A across the blood‐retina and ‐ brain barrier and developed blindness, brain anomalies and hydrocephalus. Restriction of embryonic vitamin A supply extended malformations to extra‐neuronal tissues, whereas pharmacological doses of vitamin A mitigated anomalies of STRA6‐deficient offspring. Our study established a critical role of STRA6 for retinoid homeostasis of neuronal tissues and identified the vitamin as stochastic modulator of the phenotypic characteristics of this disease.