Abstract
Neuronal ceroid lipofuscinoses (NCL) are characterized by lysosomal accumulation of autofluorescent material and lead to degeneration of the central nervous system. Patients affected by the juvenile form of NCL (JNCL), the most common form of the disease, develop visual failure prior to mental and motor deficits. It is currently unclear if the corresponding mouse model, Cln3 Δex7/8 knock-in, develops the same retinal phenotype and electroretinogram (ERG) measurements as affected patients. The aim of our study was to investigate the visual disease progression in the Cln3 Δex7/8 mice using scotopic and photopic ERGs as well as optokinetic tracking (OKT) at different ages. The results were then compared with age-matched controls.
The amplitudes of the a-wave and b-wave (scotopic ERG) decrease significantly in Cln3 Δex7/8 mice starting at the age of 12 months. A reduction in the b/a-amplitude ratio indicates a degeneration preferentially of the inner retina. An amplitude reduction observed in the Cln3 +/+ control mice may be attributed to an additional Crb1 rd8 mutation. Using optokinetic tracking (OKT) the Cln3 Δex7/8 mice show a progressive decline in visual acuity after 12 months of age.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cotman SL, Vrbanac V, Lebel LA, Lee RL, Johnson KA, Donahue LR et al (2002) Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth. Hum Mol Genet 11(22):2709–2721
Cooper JD, Russell C, Mitchison HM (2006) Progress towards understanding disease mechanisms in small vertebrate models of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1762(10):873–889
Seigel GM, Lotery A, Kummer A, Bernard DJ, Greene ND, Turmaine M et al (2002) Retinal pathology and function in a Cln3 knockout mouse model of juvenile neuronal ceroid lipofuscinosis (batten disease). Mol Cell Neurosci 19(4):515–527
Douglas RM, Alam NM, Silver BD, McGill TJ, Tschetter WW, Prusky GT (2005) Independent visual threshold measurements in the two eyes of freely moving rats and mice using a virtual-reality optokinetic system. Vis Neurosci 22(5):677–684
Prusky GT, Alam NM, Beekman S, Douglas RM (2004) Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Invest Ophthalmol Vis Sci 45(12):4611–4616
Bozorg S, Ramirez-Montealegre D, Chung M, Pearce DA (2009) Juvenile neuronal ceroid lipofuscinosis (JNCL) and the eye. Surv Ophthalmol 54(4):463–471
Staropoli JF, Haliw L, Biswas S, Garrett L, Holter SM, Becker L et al (2012) Large-scale phenotyping of an accurate genetic mouse model of JNCL identifies novel early pathology outside the central nervous system. PLoS One 7(6):e38310
Katz ML, Johnson GS, Tullis GE, Lei B (2008) Phenotypic characterization of a mouse model of juvenile neuronal ceroid lipofuscinosis. Neurobiol Dis 29(2):242–253
Mattapallil MJ, Wawrousek EF, Chan CC, Zhao H, Roychoudhury J, Ferguson TA et al (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53(6):2921–2927
Acknowledgment
We would like to thank Dr. Klaus Rüther for providing Cln3 Δex7/8 mice. We thank Dr. Frank Stehr for his support. This work was funded by the NCL-Foundation and the Auerbach foundation.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media, LLC
About this paper
Cite this paper
Volz, C., Mirza, M., Langmann, T., Jägle, H. (2014). Retinal Function in Aging Homozygous Cln3 Δex7/8 Knock-In Mice. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_63
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3209-8_63
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3208-1
Online ISBN: 978-1-4614-3209-8
eBook Packages: MedicineMedicine (R0)