Targeted disruption of the Cln3 gene provides a mouse model for Batten disease. The Batten Mouse Model Consortium [corrected]

Neurobiol Dis. 1999 Oct;6(5):321-34. doi: 10.1006/nbdi.1999.0267.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Female
  • Genotype
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Hippocampus / ultrastructure
  • Humans
  • Hypertrophy
  • Interneurons / pathology
  • Kidney / metabolism
  • Kidney / pathology
  • Male
  • Membrane Glycoproteins*
  • Mice
  • Mice, Knockout
  • Molecular Chaperones*
  • Neuronal Ceroid-Lipofuscinoses / genetics
  • Neuronal Ceroid-Lipofuscinoses / pathology*
  • Neuronal Ceroid-Lipofuscinoses / physiopathology
  • Neurons / metabolism
  • Neurons / pathology*
  • Neurons / ultrastructure
  • Proteins / genetics*
  • Proteins / physiology
  • Restriction Mapping
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • CLN3 protein, human
  • Membrane Glycoproteins
  • Molecular Chaperones
  • Proteins