CLRN1 is a gene whose mutations are associated with Usher syndrome type 3 (USH3), a condition characterized by progressive blindness and deafness [1,2,4]. The protein product of CLRN1, clarin 1, is a four-transmembrane protein predicted to be associated with ribbon synapses of photoreceptors and cochlear hair cells, and is also related to the cytoskeleton [3].

A Clrn1 knockout (KO) mouse model was created to study its function [3]. Clrn1 KO mice do not develop a retinal degeneration phenotype but show progressive loss of sensory hair cells in the cochlea and deterioration of the organ of Corti by 4 months. Hair cell stereocilia in KO animals were longer and disorganized, and some exhibited circling behavior by 5-6 months of age. This indicates that CLRN1 is unnecessary in the murine retina but essential for normal cochlear development and function [3].

In conclusion, through the Clrn1 KO mouse model, it is revealed that CLRN1 is crucial for cochlear hair cell development, and its mutation is associated with USH3. Understanding the role of CLRN1 in this way helps in comprehending the pathogenesis of Usher syndrome and may provide insights for potential treatment strategies related to this disease. [3]

References:

1. Castiglione, Alessandro, Möller, Claes. 2022. Usher Syndrome. In Audiology research, 12, 42-65. doi:10.3390/audiolres12010005. https://pubmed.ncbi.nlm.nih.gov/35076463/

2. Fuster-García, Carla, García-Bohórquez, Belén, Rodríguez-Muñoz, Ana, Millán, José M, García-García, Gema. 2021. Usher Syndrome: Genetics of a Human Ciliopathy. In International journal of molecular sciences, 22, . doi:10.3390/ijms22136723. https://pubmed.ncbi.nlm.nih.gov/34201633/

3. Geller, Scott F, Guerin, Karen I, Visel, Meike, Sankila, Eeva-Marja, Flannery, John G. 2009. CLRN1 is nonessential in the mouse retina but is required for cochlear hair cell development. In PLoS genetics, 5, e1000607. doi:10.1371/journal.pgen.1000607. https://pubmed.ncbi.nlm.nih.gov/19680541/

4. Delmaghani, Sedigheh, El-Amraoui, Aziz. 2022. The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification. In Human genetics, 141, 709-735. doi:10.1007/s00439-022-02448-7. https://pubmed.ncbi.nlm.nih.gov/35353227/