Ttll1-flox Mouse

Ttll1, short for Tubulin tyrosine ligase-like 1, is a key enzyme in the tubulin tyrosine ligase superfamily. It is involved in the post-translational polyglutamylation of tubulin in axonemal microtubules within cilia and flagella. Polyglutamylation is a dynamic process that modulates microtubule-interacting proteins and is essential for microtubule-related functions, which are crucial for various biological processes such as cell motility, neuronal development, and axonal transport [3,4].

In gene-knockout mouse models, Ttll1 deficiency leads to several phenotypes. In pcd mice (mutant of Nna1/CCP1 gene), loss of Ttll1 attenuates Purkinje cell loss and function, reduces olfactory bulb mitral cell death, and retinal photoreceptor degeneration. It also rescues impaired rhodopsin trafficking in photoreceptors [1]. In another context, Ttll1-KO mice show abnormal behaviors and an increase in glutamate in the brain, suggesting that Ttll1-mediated tubulin polyglutamylation acts as a glutamate pool in neurons [2]. Moreover, Ttll1-KO male mice exhibit chronic rhinosinusitis, otitis media, male infertility due to abnormal sperm flagella, and accumulations of exudates in the nasal passages and sinuses [4].

In conclusion, Ttll1 is essential for normal ciliary and flagellar functions, as well as for maintaining proper neuronal function. The study of Ttll1 using KO mouse models has provided insights into its role in neurodegenerative diseases, male infertility, and rhinosinusitis-related conditions, highlighting its significance in understanding these biological processes and disease mechanisms.