SLITRK6 mutations cause myopia and deafness in humans and mice
Mustafa Tekin, … , Jun Aruga, Andrew H. Crosby
Mustafa Tekin, … , Jun Aruga, Andrew H. Crosby
Published April 1, 2013
Citation Information: J Clin Invest. 2013;123(5):2094-2102. https://doi.org/10.1172/JCI65853.
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Research Article Ophthalmology

SLITRK6 mutations cause myopia and deafness in humans and mice

Abstract

Myopia is by far the most common human eye disorder that is known to have a clear, albeit poorly defined, heritable component. In this study, we describe an autosomal-recessive syndrome characterized by high myopia and sensorineural deafness. Our molecular investigation in 3 families led to the identification of 3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK-like family, member 6 (SLITRK6), a leucine-rich repeat domain transmembrane protein. All 3 mutant SLITRK6 proteins displayed defective cell surface localization. High-resolution MRI of WT and Slitrk6-deficient mouse eyes revealed axial length increase in the mutant (the endophenotype of myopia). Additionally, mutant mice exhibited auditory function deficits that mirrored the human phenotype. Histological investigation of WT and Slitrk6-deficient mouse retinas in postnatal development indicated a delay in synaptogenesis in Slitrk6-deficient animals. Taken together, our results showed that SLITRK6 plays a crucial role in the development of normal hearing as well as vision in humans and in mice and that its disruption leads to a syndrome characterized by severe myopia and deafness.

Authors

Mustafa Tekin, Barry A. Chioza, Yoshifumi Matsumoto, Oscar Diaz-Horta, Harold E. Cross, Duygu Duman, Haris Kokotas, Heather L. Moore-Barton, Kazuto Sakoori, Maya Ota, Yuri S. Odaka, Joseph Foster II, F. Basak Cengiz, Suna Tokgoz-Yilmaz, Oya Tekeli, Maria Grigoriadou, Michael B. Petersen, Ajith Sreekantan-Nair, Kay Gurtz, Xia-Juan Xia, Arti Pandya, Michael A. Patton, Juan I. Young, Jun Aruga, Andrew H. Crosby

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Figure 2

SLITRK6Q414X, SLITRK6S297X, and SLITRK6R181X are defective in cell surface localization.

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SLITRK6Q414X, SLITRK6S297X, and SLITRK6R181X are defective in cell surf...
WT SLITRK6 and mutant SLITRK6 expression vectors were transfected into HEK293 cells. Total and cell surface proteins in the transfectants were detected by antibody against the aminoterminus of SLITRK6 protein (red), whereas transfected cells were marked by GFP (green). Only WT SLITRK6 was detected at the cell surface. Scale bar: 10 μm.