Slc52a3-flox Mouse

Slc52a3, encoding riboflavin transporter protein RFVT3, is crucial for maintaining mitochondrial function as riboflavin is essential for cellular reduction-oxidation reactions [3,4,6]. It is involved in riboflavin absorption, with its deficiency potentially disrupting related physiological processes [3,4,6].

In Slc52a3 knockout (Slc52a3 -/-) mice, most died within 48 hours after birth due to hyperlipidemia, hypoglycemia, and riboflavin deficiency. Placental riboflavin transport capacity was lower in Slc52a3 -/- fetuses, and riboflavin supplementation reduced neonatal death and metabolic disorders [4]. Slc52a3 -/- embryos also showed hypoplasia of the brain and reduced thickness of cortical layers, with riboflavin supplementation rescuing the hypoplastic phenotype [8].

In humans, SLC52A3 mutations are associated with Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease, presenting with pontobulbar palsy, muscle weakness, and respiratory insufficiency [5,7]. Additionally, SLC52A3 rs13042395 C>T variation in Chinese gastric cancer patients was associated with poor survival, increased mRNA expression, and promoted cancer cell aggressiveness [1]. A meta-analysis also suggested SLC52A3 rs13042395 C>T polymorphism might be a biomarker for cancer susceptibility [2]. In esophageal cancer, SLC52A3 has two transcript variants, and its overexpression is related to disease development and patient survival, with NF-κB p65/Rel-B activating its expression [3].

In conclusion, Slc52a3 is essential for riboflavin homeostasis, which is vital for normal physiological development, including that of the brain in mice. Its disruption leads to neonatal lethality and metabolic and developmental disorders. In humans, SLC52A3 mutations and genetic variations are associated with neurological and cancer-related diseases, highlighting its significance in disease-related research. The Slc52a3 KO mouse models have been instrumental in revealing its role in these biological processes and disease conditions [1,2,3,4,5,7,8].