title: A knock-in reporter mouse model for Batten disease reveals predominant expression of Cln3 in visual, limbic and subcortical motor structures.
abstract: Juvenile neuronal ceroid lipofuscinosis (JNCL) or Batten disease is an autosomal recessive neurodegenerative disorder of children caused by mutation in CLN3. JNCL is characterized by progressive visual impairment, cognitive and motor deficits, seizures and premature death. Information about the localization of CLN3 expressing neurons in the nervous system is limited, especially during development. The present study has systematically mapped the spatial and temporal localization of CLN3 reporter neurons in the entire nervous system including retina, using a knock-in reporter mouse model. CLN3 reporter is expressed predominantly in post-migratory neurons in visual and limbic cortices, anterior and intralaminar thalamic nuclei, amygdala, cerebellum, red nucleus, reticular formation, vestibular nuclei and retina. CLN3 reporter in the nervous system is mainly expressed during the first postnatal month except in the dentate gyrus, parasolitary nucleus and retina, where it is still strongly expressed in adulthood. The predominant distribution of CLN3 reporter neurons in visual, limbic and subcortical motor structures correlates well with the clinical symptoms of JNCL. These findings have also revealed potential target brain regions and time periods for future investigations of the disease mechanisms and therapeutic intervention.
authors.affiliation: Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. songd@alleninstitute.org
authors.forename: Song-Lin
authors.initials: SL
authors.lastname: Ding
authors.forename: Luis
authors.initials: L
authors.lastname: Tecedor
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Stein
authors.forename: Beverly L
authors.initials: BL
authors.lastname: Davidson
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D055879:Gene Knock-In Techniques / Q000379:methods; D017930:Genes, Reporter; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
chemical_list: C102229:CLN3 protein, mouse; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones