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Scott H. Greenwald, Jay Neitz, Maureen Neitz; A gene replacement mouse for studying the effects of opsin gene mutations on photoreceptor structure and function. Journal of Vision 2009;9(14):40. doi: https://doi.org/10.1167/9.14.40.
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© ARVO (1962-2015); The Authors (2016-present)
We have made a targeted gene replacement mouse in which the endogenous mouse OPN1MW gene encoding the middle wavelength sensitive (M) photopigment was replaced with a “poison” variant of the human OPN1LW gene encoding long wavelength sensitive (L) photopigment that is associated with disruption of cone function in humans. This variant arose from successive recombination events that interchanged OPN1MW and OPN1LW sequences so that the dimorphic amino acid positions 153, 171, 174, 178, and 180 respectively code for Leucine, Isoleucine, Alanine, Valine, and Alanine (Carroll, Neitz, Hofer, Neitz, & Williams, 2004; Crognale et al., 2004; Neitz et al., 2004). This poisonous combination in single letter amino acid code is LIAVA. Imaging studies in humans suggest that cones expressing the LIAVA opsin develop structurally, at least to some extent, but are defective in wave-guiding light (Carroll, Neitz, Hofer, Neitz, & Williams, 2004). Our experimental question is: what happens to cones that express an LIAVA photopigment? Here, we describe the mouse model system we created to investigate the effects of expressing an LIAVA opsin on photoreceptor development, structure, and function. We also created a control mouse by replacing the endogenous mouse OPN1MW gene with a normal human OPN1LW variant known to encode a functional opsin. Comparison of the two gene replacement mouse lines promises to provide insight into the mechanisms by which substitution of amino acids from M into L pigments and vice versa disrupts photoreceptor function.
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