Ttc12-KO Mouse

Ttc12 encodes a cytoplasmic and centromere-localized protein. It plays a crucial role in the proper assembly of dynein arm complexes in motile cilia of respiratory cells and sperm flagella, thus being important for cellular motility [4].

Loss-of-function mutations in TTC12 were identified in individuals with primary ciliary dyskinesia (PCD). In sperm flagella of affected individuals, both outer and inner dynein arms (ODAs and IDAs) were absent, while in respiratory cilia, only IDAs were missing [1]. In Chinese patients with multisystem ciliopathy syndromes, compound heterozygous mutations of TTC12 were found, leading to ultrastructural defects of the inner dynein arms [2]. Also, novel homozygous TTC12 variants in infertile Chinese males caused male infertility with asthenoteratozoospermia due to dynein arm complex and mitochondrial sheath defects in flagella [3]. A novel homozygous missense TTC12 variant in an infertile Pakistani man caused severe oligoasthenoteratozoospermia and PCD, with disorganized axonemal structure in sperm flagella [4].

In conclusion, Ttc12 is essential for the assembly of dynein arm complexes in motile cilia and flagella. Research on Ttc12 loss-of-function mutations in human subjects has revealed its significant role in PCD and male infertility, highlighting its importance in understanding the genetic basis of these diseases.