Tbc1d23-flox Mouse

Tbc1d23, a member of the Tre2-Bub2-Cdc16 (TBC) family, is a Golgi-localized protein. It plays a crucial role in endosome-to-Golgi cargo trafficking, acting as a bridge between Golgi-bound golgin-97/245 and the WASH/FAM21 complex on endosomal vesicles [3,4]. It is also involved in the LKB1-AMPK signaling axis at the Golgi, which controls cellular events like polarity, proliferation, and energy homeostasis [1]. Additionally, Tbc1d23 is associated with the pathogenesis of pontocerebellar hypoplasia (PCH), a neurodevelopment disorder [1,2,5,7,8].

In zebrafish models, depletion of Tbc1d23 leads to developmental defects similar to human PCH, including hindbrain volume loss, abnormal neuronal growth, and disrupted cortical neuron positioning [7,8]. Tbc1d23 deficiency can be rescued by Golgi-targeted expression of LKB1 in zebrafish, revealing its role in the LKB1-AMPK axis at the Golgi [1]. In mice, deletion of Tbc1d23 impairs the STING-IFN-I signaling, suggesting its role in innate immunity [6].

In conclusion, Tbc1d23 is essential for endosome-to-Golgi trafficking and the LKB1-AMPK signaling at the Golgi. Its study through animal models, especially zebrafish and mice, has provided insights into its role in PCH pathogenesis and innate immunity. Understanding Tbc1d23 functions may offer new perspectives for treating related neurodevelopmental disorders and immune-related conditions.