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Mark Hassall, Alun R Barnard, Peter Charbel Issa, Robert Maclaren; Identification of a potential new mouse model of chromatopsia through spontaneous occurrence of cone pathway function loss. Invest. Ophthalmol. Vis. Sci. 2016;57(12):644.
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© ARVO (1962-2015); The Authors (2016-present)
We noticed that a particular colony of inbred mice (of 129S6/SvEvTac origin) had poor light-adapted visual responses and hypothesised that a novel genetic mutation was responsible. Retinal function was assessed by electroretinogram (ERG) recording. Test crossing was used to investigate the inheritance pattern and genetic basis of the phenotype.
We performed dark- and light-adapted electroretinogram (ERG) testing on anesthetized animals (ketamine & xylazine) using a modified Espion E3 system. 129S6/SvEvTac colony animals of both sexes were tested, at ages of post-natal day (PD) 28 to 56.An affected 129S6/SvEvTac colony animal was outcrossed to a commercially obtained, wild-type C57BL/6J mouse. All first filial generation hybrid offspring (129SB6F1) from this out-cross (n=15) underwent ERG testing at PD 36 to 64.An affected 129S6/SvEvTac animal was outcrossed with a homozygous targeted knock-out for a common achromatopsia causing gene (Cnga3-/-). All offspring of this complementation test cross (n=10) underwent ERG testing at PD 46 to 75.Chi squared test with Yates’s continuity correction was used for statistical analysis of phenotypic outcomes.
All 129S6/SvEvTac colony animals that were tested lacked cone pathway function by ERG testing (n = 9), although dark-adapted, rod-pathway based ERG responses remained intact. None of the C57BL/6 outcross F1 progeny (129SB6F1) displayed a deficit in cone ERG function (n = 15), demonstrating the phenotype is likely to be recessive (X2 = 26.1, p < 0.005). 129SB6F1 offspring are currently being intercrossed. All F1 progeny from the Cnga3 complementation test showed intact cone ERG function (n = 10), demonstrating Cnga3 is not likely the affected gene (X2 = 16.2, p < 0.005).
We have identified the spontaneous occurrence of cone pathway function loss in a line of inbred mice. Our results so far are consistent with an autosomal recessive inheritance pattern but we have excluded any involvement of Cnga3, a gene that is commonly mutated in human achromatopsia.129SB6F1 intercrossing is currently underway to confirm the inheritance pattern of the phenotype and allow the underlying mutation to be mapped and identified.Identification of new candidate genes and mouse models is important, as the genetic basis of some forms of achromatopsia remains unknown.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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