Albino Mice as an Animal Model for Infantile Nystagmus Syndrome

Traber, Ghislaine L.; Chen, Chien‐Cheng; Huang, Yingyu; Spoor, Marcella; Roos, Jeanine; Frens, Maarten A.; Straumann, Dominik; Grimm, Christian

doi:10.1167/iovs.12-10137

Cited by 18 publications

(18 citation statements)

References 86 publications

(100 reference statements)

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“…Interestingly, zebrafish and sheepdogs were for long the only animal models used in INS research but their nystagmus is not persistent under obscurity [31]. Recently, albino mice were proposed as a model for INS [32]. Melanin synthesis disorders have long been linked to visual and visuo-motor impairments and undoubtedly constitute an interesting model for INS in albinos patients (∼25% of INS patients; [33]).…”

Section: Discussionmentioning

confidence: 99%

Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse

et al. 2013

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The Aryl hydrocarbon Receptor or AhR, a ligand-activated transcription factor, is known to mediate the toxic and carcinogenic effects of various environmental pollutants such as 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). Recent studies in Caenorhabditis elegans and Drosophila melanogaster show that the orthologs of the AhR are expressed exclusively in certain types of neurons and are implicated in the development and the homeostasis of the central nervous system. While physiological roles of the AhR were demonstrated in the mammalian heart, liver and gametogenesis, its ontogenic expression and putative neural functions remain elusive. Here, we report that the constitutive absence of the AhR in adult mice (AhR−/−) leads to abnormal eye movements in the form of a spontaneous pendular horizontal nystagmus. To determine if the nystagmus is of vestibular, visual, or cerebellar origin, gaze stabilizing reflexes, namely vestibulo-ocular and optokinetic reflexes (VOR and OKR), were investigated. The OKR is less effective in the AhR−/− mice suggesting a deficit in the visuo-motor circuitry, while the VOR is mildly affected. Furthermore, the AhR is expressedin the retinal ganglion cells during the development, however electroretinograms revealed no impairment of retinal cell function. The structure of the cerebellum of the AhR−/− mice is normal which is compatible with the preserved VOR adaptation, a plastic process dependent on cerebellar integrity. Finally, intoxication with TCDD of control adults did not lead to any abnormality of the oculomotor control. These results demonstrate that the absence of the AhR leads to acquired central nervous system deficits in the adults. Given the many common features between both AhR mouse and human infantile nystagmus syndromes, the AhR−/− mice might give insights into the developmental mechanisms which lead to congenital eye disorders.

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Section: Discussionmentioning

confidence: 99%

Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse

et al. 2013

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“…The mechanisms leading to nystagmus during development are not clear and several mechanisms have been suggested (Gottlob and Proudlock, ). Animal models with various alterations in chiasmatic routing such as in belladonna zebrafish mutant (achiasma in a model with normally only crossed projection), Shh mutant mice (achiasma) and albino mice all lead to nystagmus (Huang et al, ; Traber et al, ), suggesting that the miswiring of RGCs could be the origin of nystagmus, although no clear mechanism has yet been identified. Another hypothesis is that, in addition to retinal defects, there is an abnormal development of binocular cortical motor system controlling the optokinetic system (Brodsky and Dell'Osso, ).…”

Section: Disorders Associated With Misrouted Retinal Axonsmentioning

confidence: 99%

“…The mechanisms leading to nystagmus during development are not clear and several mechanisms have been suggested (Gottlob and Proudlock, 2014). Animal models with various alterations in chiasmatic routing such as in belladonna zebrafish mutant (achiasma in a model with normally only crossed projection), Shh mutant mice (achiasma) and albino mice all lead to nystagmus (Huang et al, 2006;Traber et al, 2012), suggesting that the miswiring of Figure 3 Visual field representations in achiasmatic and albino humans. In control subjects, each binocular hemifield (yellow and blue) is represented into different parts of the retina.…”

Section: Nystagmus In Achiasma and Albinismmentioning

confidence: 99%

Retinal axon guidance at the midline: Chiasmatic misrouting and consequences

Prieur

Rebsam

2017

Developmental Neurobiology

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The visual representation of the outside world relies on the appropriate connectivity between the eyes and the brain. Retinal ganglion cells are the sole neurons that send an axon from the retina to the brain, and thus the guidance decisions of retinal axons en route to their targets in the brain shape the neural circuitry that forms the basis of vision. Here, we focus on the choice made by retinal axons to cross or avoid the midline at the optic chiasm. This decision allows each brain hemisphere to receive inputs from both eyes corresponding to the same visual hemifield, and is thus crucial for binocular vision. In achiasmatic conditions, all retinal axons from one eye project to the ipsilateral brain hemisphere. In albinism, abnormal guidance of retinal axons at the optic chiasm leads to a change in the ratio of contralateral and ipsilateral projections with the consequence that each brain hemisphere receives inputs primarily from the contralateral eye instead of an almost equal distribution from both eyes in humans. In both cases, this misrouting of retinal axons leads to reduced visual acuity and poor depth perception. While this defect has been known for decades, mouse genetics have led to a better understanding of the molecular mechanisms at play in retinal axon guidance and at the origin of the guidance defect in albinism. In addition, fMRI studies on humans have now confirmed the anatomical and functional consequences of axonal misrouting at the chiasm that were previously only assumed from animal models. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 844-860, 2017.

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“…The optokinetic reflex (OKR), a basal mechanism to stabilise the image of the environment on the retina is altered or even completely absent in albino mammals (e.g. mouse: Balkema et al ., ; Traber et al ., ; Yeritsyan et al ., ; rat: Precht & Cazin, ; Sirkin et al ., ; rabbit: Hahnenberger, ; Collewijn et al ., ; ferret: Hoffmann et al ., ; human: St. John et al ., ; Collewijn et al ., ; Abadi & Pascal, ). A linkage analysis of the optokinetic blind phenotype in BALB/c mice indicates a recessive, monogenic mode of inheritance.…”

Section: Introductionmentioning

confidence: 99%

Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction‐selective

Krause

Distler

Hoffmann

2014

Eur J of Neuroscience

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The optokinetic deficits in albinotic rats and ferrets are caused by the loss of direction selectivity in the accessory optic system (AOS). However, the underlying mechanisms for this loss are still not clear. Here we tested the hypothesis that, in albino rats, the retinal input to the AOS lacks direction selectivity and, as a consequence, neurons in the AOS are direction non-selective. We investigated ON-center direction-selective retinal ganglion cells, the major input to the AOS, in pigmented Long Evans and albino Wistar rats using extracellular in vitro patch-clamp techniques. To visualise putative AOS-projecting direction-selective ganglion cells, we retrogradely labeled them by injection of the infrared-sensitive dye indocyanine green into the medial terminal nucleus of the AOS. The present study is the first to present physiological evidence for retinal ON-center direction-selective ganglion cells in rat. Our results show that, in albinotic and pigmented rats, ON-center retinal ganglion cells projecting to the AOS are similarly direction-selective, suggesting that the optokinetic deficit must be caused by the abolition of direction selectivity in the AOS itself.

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Albino Mice as an Animal Model for Infantile Nystagmus Syndrome

Abstract: Based on our results, we endorse the investigated albino mouse strains as new animal models for INS.

Cited by 18 publications

References 86 publications

Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse

Oculomotor Deficits in Aryl Hydrocarbon Receptor Null Mouse

Retinal axon guidance at the midline: Chiasmatic misrouting and consequences

Retinal ganglion cells projecting to the accessory optic system in optokinetic blind albinotic rats are direction‐selective

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