Rfx3-flox Mouse

Rfx3, or Regulatory Factor X 3, is a major transcription factor essential for ciliogenesis and cilia functions [2]. It also regulates pancreatic islet cell differentiation and mature β -cell functions [2]. RFX genes, including Rfx3, are evolutionarily conserved transcription factors acting as master regulators of central nervous system development and ciliogenesis [1].

In mouse models, Rfx3 -deficient mice exhibit left-right asymmetry defects due to a pronounced defect in nodal cilia, indicating its role in nodal cilium development and left-right asymmetry specification [4]. Pancreatic islets of perinatal Rfx3(-/-) mice show a marked reduction in insulin-producing beta-cells, with defective beta-cells exhibiting reduced insulin, Glut-2, and Gck expression, leading to glucose intolerance [5]. In human studies, deleterious variants in Rfx3 are associated with autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) [1]. Loss of Rfx3 in human induced pluripotent stem cell-derived pancreatic islet organoids disrupts pancreatic endocrine gene regulation, reduces hormone-secreting islet cells, and impairs beta cell function and insulin secretion [3].

In conclusion, Rfx3 is crucial for ciliogenesis, pancreatic islet cell differentiation, and central nervous system development. Mouse models, especially Rfx3 knockout models, have revealed its role in diseases such as left-right asymmetry defects, glucose intolerance, and neurodevelopmental disorders like ASD, intellectual disability, and ADHD. These findings enhance our understanding of related biological processes and disease mechanisms.