Phenotypes Associated with This Genotype

Genotype
MGI:5296507

• Allelic Composition: Gfap^tm1Pkny/Gfap^tm1Pkny; Ppt1^tm1Hof/Ppt1^tm1Hof; Vim^tm1Cba/Vim^tm1Cba
• Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:177265 )

nervous system

brain inflammation ( J:177265 )

• 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

abnormal nervous system morphology ( J:177265 )

• triple mutants exhibit earlier and more rapid progression of neurodegenerative disorder resembling infantile neuronal ceroid lipofuscinosis than single Ppt1 homozygotes

abnormal brain morphology ( J:177265 )

• mutants exhibit a 3.3-fold increase in autofluorescent accumulation in the brain compared to wild-type mice

decreased brain weight ( J:177265 )

• decrease in brain weight by 26.2% is seen by 6 months of age

abnormal visual cortex morphology ( J:177265 )

• atrophy of the primary visual cortex

thin cerebral cortex ( J:177265 )

• at 6 months of age, 28.9% decrease in cortical thickness

brain atrophy ( J:177265 )

• by 5 months of age, brain atrophy is apparent

neurodegeneration ( J:177265 )

• 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

hippocampal neuron degeneration ( J:177265 )

immune system

abnormal cytokine level ( J:177265 )

• 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.

brain inflammation ( J:177265 )

• 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

abnormal cytokine level ( J:177265 )

• 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.