Mak-KO Mouse

Mak, a ciliopathy kinase, is a ciliary tip-localized intraflagellar transport (IFT) regulator. IFT is crucial for the formation, function, and maintenance of primary cilia, whose dysfunction leads to ciliopathies in humans. Mak cooperates with another IFT regulator, the ciliopathy kinase Ick, and together they are essential for the maintenance of retinal photoreceptors [1].

Simultaneous disruption of Mak and Ick in mice resulted in the loss of photoreceptor ciliary axonemes and severe retinal degeneration. In Mak -/- mice, gene delivery of Ick and pharmacological inhibition of FGF receptors (Ick negative regulators) ameliorated retinal degeneration. Additionally, Ccrk kinase was identified as an upstream activator of Mak and Ick in retinal photoreceptor cells. Overexpression of Mak, Ick, and Ccrk along with pharmacological inhibition of FGF receptors suppressed ciliopathy-related phenotypes caused by cytoplasmic dynein inhibition in cultured cells [1].

In conclusion, Mak, through its cooperation with Ick and regulation by Ccrk, is essential for maintaining the integrity of retinal photoreceptors. The study of Mak knockout mouse models has revealed its critical role in preventing retinal degeneration, offering potential therapeutic approaches for retinitis pigmentosa caused by MAK mutations [1].

References:

1. Chaya, Taro, Maeda, Yamato, Tsutsumi, Ryotaro, Tanaka, Teruyuki, Furukawa, Takahisa. 2024. Ccrk-Mak/Ick signaling is a ciliary transport regulator essential for retinal photoreceptor survival. In Life science alliance, 7, . doi:10.26508/lsa.202402880. https://pubmed.ncbi.nlm.nih.gov/39293864/