Journal article
A Knock-In Reporter Model of Batten Disease
The Journal of neuroscience, Vol.27(37), pp.9826-9834
09/12/2007
DOI: 10.1523/JNEUROSCI.1710-07.2007
PMCID: PMC6672654
PMID: 17855597
Abstract
Juvenile neuronal ceroid lipofuscinosis is a severe inherited neurodegenerative disease resulting from mutations in
CLN3
(ceroid-lipofuscinosis, neuronal 3, juvenile). CLN3 function, and where and when it is expressed during development, is not known. In this study, we generated a knock-in reporter mouse to elucidate CLN3 expression during embryogenesis and after birth and to correlate expression and behavior in a CLN3-deficient mouse. In embryonic brain, expression appeared in the cortical plate. In postnatal brain, expression was prominent in the cortex, subiculum, parasubiculum, granule neurons of the dentate gyrus, and some brainstem nuclei. In adult brain, reporter gene expression waned in most areas but remained in vascular endothelia and the dentate gyrus. Mice homozygous for
Cln3
deletion showed two hallmark pathological features of the neuronal ceroid lipofuscinosises: autofluorescent inclusions and lysosomal enzyme elevation. Moreover, CLN3-deficient reporter mice displayed progressive neurological deficits, including impaired motor function, decreased overall activity, acquisition of resting tremors, and increased susceptibility to pentilentetrazole-induced seizures. Notably, seizure induction in heterozygous mice was accompanied by enhanced reporter expression. This model provides us with the unique ability to correlate expression with pathology and behavior, thus facilitating the elucidation of CLN3 function and the pathogenesis of Batten disease.
Details
- Title: Subtitle
- A Knock-In Reporter Model of Batten Disease
- Creators
- Steven L. Eliason - University of IowaColleen S. Stein - University of IowaQinwen Mao - University of IowaLuis Tecedor - University of IowaSong-Lin Ding - Departments of Internal MedicineD. Meredith Gaines - University of IowaBeverly L. Davidson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.27(37), pp.9826-9834
- DOI
- 10.1523/JNEUROSCI.1710-07.2007
- PMID
- 17855597
- PMCID
- PMC6672654
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Society for Neuroscience
- Language
- English
- Date published
- 09/12/2007
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984618650302771
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