Combining two gene mutations in mice restores cell structures and fixes sensory problems

Mutations in the centrosomal protein CEP290 are associated with distinct clinical manifestations, including Leber congenital amaurosis (LCA), a hereditary cause of blindness.

• Defects in cilia biogenesis and transport can lead to various human ciliopathies due to mutations in over 30 different genes.
• Mice with a mutant Cep290 allele show early-onset retinal degeneration similar to LCA, linked to a specific deletion in the CEP290 protein.
• The deleted domain of the CEP290 protein interacts with the MKKS protein, mutations of which are found in patients with Bardet-Biedl syndrome.
• Knockdown of mkks and cep290 in zebrafish embryos results in sensory defects in the eye and inner ear.
• Combining Cep290rd16 and Mkksko alleles in mice leads to enhanced ciliogenesis and improved sensory functions compared to single mutations.
• Alterations in the interaction between CEP290 and MKKS may impact the stability of protein complexes at the cilia transition zone.

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