Mouse Genome Informatics
cx
    Gfaptm1Pkny/Gfaptm1Pkny
Ppt1tm1Hof/Ppt1tm1Hof
Vimtm1Cba/Vimtm1Cba

involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging

nervous system
• mutants exhibit immune cell infiltration in the brain, with an increase in CD45+ leukocytes, CD3+ T-cells, and CD68+ large monocytes; immune cell infiltration in triple mutants is similar to that in single Ppt1 homozygotes
• triple mutants exhibit earlier and more rapid progression of neurodegenerative disorder resembling infantile neuronal ceroid lipofuscinosis than single Ppt1 homozygotes
• mutants exhibit a 3.3-fold increase in autofluorescent accumulation in the brain compared to wild-type mice
• decrease in brain weight by 26.2% is seen by 6 months of age
• atrophy of the primary visual cortex
• at 6 months of age, 28.9% decrease in cortical thickness
• by 5 months of age, brain atrophy is apparent
• mutants exhibit progressive neurodegeneration, with degenerating neurons within the cortex, thalamus, hippocampus, and cerebellum at 5 months of age
• at 5 months of age, extent of neurodegeneration is similar to that seen in single Ppt1 mutants at 7 months of age

immune system
• mutants exhibit elevated cytokine levels, starting at 1 month of age, with an increase in the number of different cytokines elevated by 3 and 6 months of age
• at 1 month of age, cytokines RANTES and oncostatin-M are elevated compared to wild-type or single Ppt1 homozygotes
• at 3 months of age, IFN-gamma, TNF-alpha, oncostatin-M, lymphoactin, GM-CSF, RANTES, IP-10, MIP-1beta, MIP-2, MCP-1, MCP-3, and MCP-5 are elevated compared to wild-type mice; more cytokines and chemokines are elevated at 3 months of age than in single Ppt1 homozygotes.
• mutants exhibit immune cell infiltration in the brain, with an increase in CD45+ leukocytes, CD3+ T-cells, and CD68+ large monocytes; immune cell infiltration in triple mutants is similar to that in single Ppt1 homozygotes

homeostasis/metabolism
• mutants exhibit elevated cytokine levels, starting at 1 month of age, with an increase in the number of different cytokines elevated by 3 and 6 months of age
• at 1 month of age, cytokines RANTES and oncostatin-M are elevated compared to wild-type or single Ppt1 homozygotes
• at 3 months of age, IFN-gamma, TNF-alpha, oncostatin-M, lymphoactin, GM-CSF, RANTES, IP-10, MIP-1beta, MIP-2, MCP-1, MCP-3, and MCP-5 are elevated compared to wild-type mice; more cytokines and chemokines are elevated at 3 months of age than in single Ppt1 homozygotes.

Mouse Models of Human Disease
OMIM IDRef(s)
Ceroid Lipofuscinosis, Neuronal, 3; CLN3 204200 J:177265