Mouse Genome Informatics
hm
    Cln3tm1.1Mem/Cln3tm1.1Mem
involves: 129S/SvEv * CD-1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• homozygotes show reduced (80%) survival, with the earliest death occurring at 7 months of age

behavior/neurological
N
• no handling-induced seizures are observed (J:79615)
• at 10-12 months, tail hang/clasping assays revealed clasping in 42% of homozygous mutant mice, compared with 10% of wild-type or heterozygous mutant mice
• at 10-12 months, gait analyses indicated shortened average stride length (rear paw) and increased base width (rear paw stance)
• at 10 -12 months of age

liver/biliary system
• in liver, ATP synthase subunit c-reactive deposition is observed as early as E19.5
• at 10 months, mutant hepatocytes contain abundant autofluorescent, ATP synthase subunit c-reactive membrane deposits

vision/eye
• retinal neurons contain membrane deposits in the RGC layer and the inner nuclear layer (INL), with small punctate granules in the outer nuclear layer (ONL)
• retinal deposits are first observed at P1.5, within the neuroblastic layer
• punctate subunit c-reactive granules are noted within the ONL and INL in the mature retina at P8 and P30
• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes
• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile
• retinas from pigmented homozygotes do not exhibit a cone cell loss at 10-17 months, suggesting that hypopigmentation may accelerate retinal degeneration

nervous system
• at 10 months, homozygotes display membranous deposits in the CNS
• autofluorescent, ATP synthase subunit c-reactive membrane deposits are observed in the cytoplasm of CA2 and CA3 pyramidal cells of the hippocampus, Purkinje cells of the cerebellum, as well as cortical neurons and thalamic neurons
• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle
• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8
• ultrastructurally, CA2/3 hippocampal pyramidal neurons show abundant perinuclear, osmiophilic and electron-dense inclusions
• such subunit-c inclusions have multilamellar membranes, a JNCL-like 'fingerprint' appearance, and are first detected at P8, increasing in size and intensity by P30
• cerebellar deposits are detected in the Purkinje cell layer at E19.5, increasing in severity by P30
• accumulates are first noted at E19.5 in neurons of the dentate gyrus and in the subventricular zone at the lateral ventricle
• in these regions, ATP synthase subunit c-reactive deposits are undetectable after P8
• at 10 months, all homozygotes exhibit reactive gliosis in the motor cortex, white matter tracts of the cerebellum and midbrain, including the inferior colliculus
• no apoptotic changes are observed in these regions
• at 10-17 months, retinas of hypopigmented homozygotes show a 37% reduction in the number of cone cells per field relative to retinas of hypopigmented heterozygotes
• retinal ganglion cells show electron-dense membranous perinuclear inclusions with a JNCL-like 'fingerprint' profile

Mouse Models of Human Disease
OMIM IDRef(s)
Ceroid Lipofuscinosis, Neuronal, 3; CLN3 204200 J:79615