Eye diseases in mice show strong co-morbidity with alterations in their behaviour.
Eye diseases in mice show strong co-morbidity with alterations in their behaviour.
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Original abstract
Introduction: Many genes that are active during eye development are also expressed in the brain. Therefore we tested the hypothesis that alterations in the structure and function of the eye are associated with changes in the behaviour of the same mice. Materials & Methods: To test this hypothesis, we used phenotypic annotations from 294 mutant mouse lines taken from the public Phenomap database (as of Nov. 30, 2015) of the German Mouse Clinic (http://www.mouseclinic.de/phenomap/phenomap.html) representing the overall assessment of more than 7 million single phenotypic records. We analyzed the frequency of clearly altered phenotypes in the eye and compared this to clear phenotypic differences between wild-type and mutants observed in other routine screens of the German Mouse Clinic. Results: 36 (12.2%) of the 294 mutant mouse lines of the Phenomap database showed a clearly changed phenotype affecting eye and vision. It is surprising that 3 of the 36 affected genes are not yet listed in OMIM, and just in 11 of the 36 genes mutations are known to be causative for human diseases. For the other 25 genes (=70%) no human disorder has been described so far. Among these 36 mutant lines, 23 lines showed also clear differences to the wild-type phenotype in behaviour and clinical chemistry; an overlap to changes in neurological phenotypes is given in 17 mutant lines indicating that eye diseases might be used as biomarkers for neurological or psychiatric diseases. Among the three mutant lines whose genes are not listed in OMIM (Wsb2, Spryd3 and Zfp119a), Wsb2 (WD repeat and SOCS box-containing 2) and Spryd3 (SPRY domain containing 3) showed alterations in their behaviour and in neurological features beside the eye: the Wsb2 mutants showed thinner retinae and a reduced number of fundic blood vessels, decreased rearing activity in the open field (exploratory behaviour), decreased acoustic reactivity and more tail elevation. The Spryd3 mutants showed reduced eye size, sex-specific changes in the locomotor activity, increased center time (indicating decreased anxiety) and decreased prepulse inhibition (indicating alteration in sensorimotor gating like in schizophrenia). Conclusions: In humans, eye diseases can be observed much easier than behavioural alterations; examples for this aspect have been previously discussed for PITX3 for cataracts and Parkinson’s disease and CRYBB1 or CRYBB2 for schizophrenia (Graw, J.: Exp Eye Res. 2015; doi: 10.1016/j.exer.2015.11.006. Therefore, ophthalmologists might be aware of neurological problems in their patients.