title: Targeted disruption of the Cln3 gene provides a mouse model for Batten disease. The Batten Mouse Model Consortium [corrected].
abstract: Batten disease, a degenerative neurological disorder with juvenile onset, is the most common form of the neuronal ceroid lipofuscinoses. Mutations in the CLN3 gene cause Batten disease. To facilitate studies of Batten disease pathogenesis and treatment, a murine model was created by targeted disruption of the Cln3 gene. Mice homozygous for the disrupted Cln3 allele had a neuronal storage disorder resembling that seen in Batten disease patients: there was widespread and progressive intracellular accumulation of autofluorescent material that by EM displayed a multilamellar rectilinear/fingerprint appearance. Inclusions contained subunit c of mitochondrial ATP synthase. Mutant animals also showed neuropathological abnormalities with loss of certain cortical interneurons and hypertrophy of many interneuron populations in the hippocampus. Finally, as is true in Batten disease patients, there was increased activity in the brain of the lysosomal protease Cln2/TPP-1. Our findings are evidence that the Cln3-deficient mouse provides a valuable model for studying Batten disease.
authors.affiliation: Royal Free and University College London Medical School, Rayne Institute, University Street, London, WC1E 6JJ, United Kingdom.
authors.forename: H M
authors.initials: HM
authors.lastname: Mitchison
authors.forename: D J
authors.initials: DJ
authors.lastname: Bernard
authors.forename: N D
authors.initials: ND
authors.lastname: Greene
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.forename: M A
authors.initials: MA
authors.lastname: Junaid
authors.forename: R K
authors.initials: RK
authors.lastname: Pullarkat
authors.forename: N
authors.initials: N
authors.lastname: de Vos
authors.forename: M H
authors.initials: MH
authors.lastname: Breuning
authors.forename: J W
authors.initials: JW
authors.lastname: Owens
authors.forename: W C
authors.initials: WC
authors.lastname: Mobley
authors.forename: R M
authors.initials: RM
authors.lastname: Gardiner
authors.forename: B D
authors.initials: BD
authors.lastname: Lake
authors.forename: P E
authors.initials: PE
authors.lastname: Taschner
authors.forename: R L
authors.initials: RL
authors.lastname: Nussbaum
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D006984:Hypertrophy; D007395:Interneurons / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D018832:Molecular Chaperones; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000091346:Tripeptidyl-Peptidase 1
chemical_list: C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011506:Proteins; C000717268:Tpp1 protein, mouse; D000091346:Tripeptidyl-Peptidase 1; C000717267:TPP1 protein, human