Phenotypes associated with this allele

• Allele Symbol: Ppt1^tm1Hof
• Allele Name: targeted mutation 1, Sandra L Hoffmann
• Allele ID: MGI:2176390
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ppt1^tm1Hof/Ppt1^tm1Hof	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:5296508
hm2	Ppt1^tm1Hof/Ppt1^tm1Hof	involves: 129S6/SvEvTac * C57BL/6J	MGI:2176410
cx3	Gfap^tm1Pkny/Gfap^tm1Pkny Ppt1^tm1Hof/Ppt1^tm1Hof Vim^tm1Cba/Vim^tm1Cba	involves: 129P2/OlaHsd * 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:5296507

Genotype
MGI:5296508

hm1

• Allelic Composition: Ppt1^tm1Hof/Ppt1^tm1Hof
• 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 )

• mutants die by 35 weeks of age, with a median survival of 33 weeks

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

abnormal brain morphology ( J:177265 )

• mutants exhibit a 2.6-fold increase in autofluorescent accumulation in the brain compared to wild-type mice

decreased brain weight ( J:177265 )

• decrease in brain weight by 13.4% 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, 21.6% decrease in cortical thickness

brain atrophy ( J:177265 )

• by 5 months of age, brain atrophy is apparent

astrocytosis ( J:177265 )

• reactive astrocytosis

neurodegeneration ( J:177265 )

• mutants exhibit progressive neurodegeneration, with degenerating neurons within the corpus callosum, hippocampus, and thalamus at 5 months of age

hippocampal neuron degeneration ( J:177265 )

homeostasis/metabolism

abnormal cytokine level ( J:177265 )

• mutants exhibit elevated cytokine and chemokine levels at 3 months of age

• fewer cytokines and chemokines are elevated in single mutant mice than in triple Ppt1, Gfap and Vim homozygotes

immune system

abnormal cytokine level ( J:177265 )

• mutants exhibit elevated cytokine and chemokine levels at 3 months of age

• fewer cytokines and chemokines are elevated in single mutant mice than in triple Ppt1, Gfap and Vim 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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 1		DOID:0110721	OMIM:256730	J:177265

Genotype
MGI:2176410

hm2

• Allelic Composition: Ppt1^tm1Hof/Ppt1^tm1Hof
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

Neuronal loss is Ppt1^tm1Hof/Ppt1^tm1Hof mice

mortality/aging

premature death ( J:72931 )

• death by 10 months of age

nervous system

myoclonus ( J:72931 )

• evident beginning at 3 to 4 months of age

microgliosis ( J:280337 )

• early onset in the retina

abnormal brain morphology ( J:72931 )

• autofluorescent deposits, granular osmiophilic deposits, found in cells throughout brain

• storage at 5 months of age found in cerebral cortex, cerebellar Purkinje and granular layers, hippocampus, thalamus and hypothalamus, dentate nucleus, pons, and some areas of the medulla

decreased brain size ( J:72931 )

astrocytosis ( J:280337 )

• early onset in the retina

decreased retina photoreceptor cell number ( J:280337 )

• at P240

decreased retina cone cell number ( J:280337 )

• at P112 and P240, but not at P45

abnormal retina cone bipolar cell morphology ( J:280337 )

• reduced number at P112 and P240

abnormal retina rod bipolar cell morphology ( J:280337 )

• reduced number at P240

neurodegeneration ( J:72931 )

• cerebral cortex neurodegeneration

hippocampal neuron degeneration ( J:72931 )

Purkinje cell degeneration ( J:72931 )

retina ganglion cell degeneration ( J:280337 )

• at P240, but not P45 and P112

retina photoreceptor degeneration ( J:280337 )

• at P240

vision/eye

decreased retina photoreceptor cell number ( J:280337 )

• at P240

decreased retina cone cell number ( J:280337 )

• at P112 and P240, but not at P45

abnormal retina cone bipolar cell morphology ( J:280337 )

• reduced number at P112 and P240

abnormal retina rod bipolar cell morphology ( J:280337 )

• reduced number at P240

retina ganglion cell degeneration ( J:280337 )

• at P240, but not P45 and P112

retina photoreceptor degeneration ( J:280337 )

• at P240

thin retina inner nuclear layer ( J:280337 )

• at P240

thin retina outer nuclear layer ( J:280337 )

• at P240

decreased total retina thickness ( J:280337 )

• at P240

retina deposits ( J:280337 )

• accumulation of granular osmiophilic storage material (e.g. saposin D, electron-dense storage material) in subretinal microglia and macrophages

retina gliosis ( J:280337 )

• slightly at P45 and P112, strongly at P240 as measured by mean intensity

• significantly at P112 and P240 as measured by integrated density values

behavior/neurological

abnormal aggression-related behavior ( J:72931 )

• bite wounds in colony evident

decreased grooming behavior ( J:72931 )

• beginning at 4 to 5 months of age

jerky movement ( J:72931 )

abnormal gait ( J:72931 )

• lowering of pelvis, splayed hind limbs, hunched posture, side-to-side wobbling, evident beginning at 4 - 5 months of age and progressing to hind limb paralysis

hindlimb paralysis ( J:72931 )

• end point of abnormal gait

myoclonus ( J:72931 )

• evident beginning at 3 to 4 months of age

muscle

myoclonus ( J:72931 )

• evident beginning at 3 to 4 months of age

skeleton

thick neurocranium ( J:72931 )

• thickened

craniofacial

thick neurocranium ( J:72931 )

• thickened

hematopoietic system

microgliosis ( J:280337 )

• early onset in the retina

immune system

microgliosis ( J:280337 )

• early onset in the retina

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 3		DOID:0110731	OMIM:204200	J:72931

Genotype
MGI:5296507

cx3

• 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

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.