Tbc1d32-flox Mouse

Tbc1d32, also known as BROMI, is a gene involved in the development and function of cilia. It interacts with proteins like CCRK/CDK20 and FAM149B1/JBTS36 to regulate intraflagellar transport turnaround involving ICK/CILK1, which is crucial for cilia-related processes [3]. It is also implicated in pathways such as Sonic Hedgehog (Shh) signaling [4].

In loss-of-function studies, Tbc1d32 variants have been associated with multiple diseases. In humans, biallelic loss-of-function variants in Tbc1d32 underlie syndromic hypopituitarism, potentially via disrupted Shh signaling [4]. Variants in Tbc1d32 disrupt retinal ciliogenesis, leading to retinitis pigmentosa, with defects in photoreceptor differentiation and retinoid cycling [1,5]. Also, rare likely pathogenic variants in Tbc1d32 segregate with recessive disease, expanding the phenotypic spectrum of a complex ciliopathy, including a severe prenatal phenotype [2].

In conclusion, Tbc1d32 plays a critical role in cilia-related biological processes and is associated with diseases such as retinitis pigmentosa, syndromic hypopituitarism, and ciliopathies. Functional studies, especially those involving loss-of-function models, have been instrumental in revealing these associations, providing insights into the underlying disease mechanisms.