2700049A03Rik, also known as Talpid3 in mouse (and KIAA0856 in human), is a gene encoding a centrosomal protein essential for the assembly of primary cilia [2]. It is associated with pathways related to cilia formation and plays a crucial role in normal cellular and tissue development, especially in the central nervous system. Mouse models are valuable for studying its function.

In a study on renal ischemia reperfusion injury, the promoter methylation of 2700049A03Rik was found to be altered following renal injury, and this methylation was negatively correlated with its mRNA expression in renal tissues [1]. In a conditional knockout (CKO) mouse model of Joubert syndrome, deletion of conserved exons 11-12 of Talpid3 (2700049A03Rik) in the central nervous system recapitulated the complete cerebellar phenotype seen in the disease. The mutant mice showed progressive ataxia, severely hypoplastic cerebellar hemispheres and vermis, abnormal decussation of the superior cerebellar peduncles, disorganized Purkinje cell layer, thinner external granule layer lacking primary cilia, reduced proliferation, ectopic clusters of mature granule neurons, abnormal synapses, and cell disorientation in the external granule layer. Also, there was a reduction in Wnt7a expression, suggesting roles in both Hedgehog and other pathways [2].

In conclusion, 2700049A03Rik is essential for primary cilia assembly. Its KO/CKO mouse models have revealed its role in renal ischemia reperfusion injury through epigenetic regulation, and in Joubert syndrome, highlighting its importance in cerebellar development and associated disease mechanisms. [1,2]