Phenotypes associated with this allele

• Allele Symbol: Tpp1^tm1Plob
• Allele Name: targeted mutation 1, Peter Lobel and David Sleat
• Allele ID: MGI:3521972
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tpp1^tm1Plob/Tpp1^tm1Plob	B6.129S1-Tpp1^tm1Plob	MGI:3804722
hm2	Tpp1^tm1Plob/Tpp1^tm1Plob	involves: 129S1/Sv	MGI:3522158
hm3	Tpp1^tm1Plob/Tpp1^tm1Plob	involves: 129S1/Sv * C57BL/6	MGI:3522157
ht4	Tpp1^tm1Plob/Tpp1^tm1.1Plob	B6.129S1-Tpp1^tm1Plob/Tpp1^tm1.1Plob	MGI:3804729

Genotype
MGI:3804722

hm1

• Allelic Composition: Tpp1^tm1Plob/Tpp1^tm1Plob
• Genetic Background: B6.129S1-Tpp1^tm1Plob

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

mortality/aging

premature death ( J:136105 )

• Background Sensitivity: survival to an average age of 132 days (135-138), shorter than on a 129S1/Sv background

behavior/neurological

tremors ( J:136105 )

• a constant tremor is noticeable around 7 weeks of age which becomes more pronounced with age

ataxia ( J:136105 )

• mutants eventually develop ataxia and abnormal gait

abnormal gait ( J:136105 )

• at around 4 months of age, mutants show a shortened stride with splaying of the rear limbs

short stride length ( J:136105 )

nervous system

abnormal brain morphology ( J:136105 )

• accumulation of a small proteolipid, subunit C of mitochondrial ATP synthase (SCMAS) in the brain is detected by 60 days of age and increases as mice age

abnormal Purkinje cell morphology ( J:136105 )

• levels of SCMAS are elevated in the Purkinje cell layer of the cerebellar cortex at 4 months of age

cellular

abnormal lysosome morphology ( J:136105 )

• significant accumulation of punctuate cytoplasmic autofluorescent lysosomal storage material in the cerebral cortex at 128 days of age

abnormal lysosome physiology ( J:136105 )

• significant accumulation of punctuate cytoplasmic autofluorescent lysosomal storage material in the cerebral cortex at 128 days of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 2		DOID:0110726	OMIM:204500	J:136105

Genotype
MGI:3522158

hm2

• Allelic Composition: Tpp1^tm1Plob/Tpp1^tm1Plob
• Genetic Background: involves: 129S1/Sv

mortality/aging

premature death ( J:94884 , J:136105 )

• Background Sensitivity: survival to an average of 164 days, with most dying between 136-185 days of age; survival is slightly longer than on a mixed 129S1/Sv and C57BL/6 background (J:94884)

Genotype
MGI:3522157

hm3

• Allelic Composition: Tpp1^tm1Plob/Tpp1^tm1Plob
• Genetic Background: involves: 129S1/Sv * C57BL/6

mortality/aging

premature death ( J:94884 )

• Background Sensitivity: survival to an average of 138 days, with most dying between 108-169 days of age; survival is slightly shorter than on a 129S1/Sv background

behavior/neurological

tremors ( J:94884 )

• slight, constant tremor develops at 7 weeks of age; increasing severity with age

ataxia ( J:94884 )

• observed with advanced age

impaired coordination ( J:94884 )

• in a rotarod test, activity of mutants was normal until 14 weeks of age, then became severely reduced in ability compared to controls

• in a rocking rotating rod test, impaired performance was noted after 10 weeks of age

abnormal gait ( J:94884 )

• observed with advanced age; hunched gait with outward pointing feet and splayed hind limbs and side to side shaking while walking

decreased vertical activity ( J:94884 )

• decreased rearing activity

audiogenic seizures ( J:94884 )

• apparent fatal startle seizures were observed that were induced by stimuli such as a loud noise

cellular

abnormal lysosome physiology ( J:94884 )

• accumulation of ceroid lipofuscin within the lysosomal compartment was observed from 48 days of age in neocortex samples; accumulation of additional material was seen with age; also observed in most other brain regions

• accumulation of curvilinear storage bodies was apparent in cortex at 35 days of age; was also observed in other tissues, but without overt cytopathology

nervous system

audiogenic seizures ( J:94884 )

• apparent fatal startle seizures were observed that were induced by stimuli such as a loud noise

neurodegeneration ( J:94884 )

• neuronal degeneration of particular brain areas was observed; these areas include auditory pathways but not visual pathways

• mild atrophy of forebrain structures including the hippocampus and overlying neocortex; loss of neurons

Purkinje cell degeneration ( J:94884 )

• variable in extent and with age; most prominent in lobules III and IV of the cerebellum

demyelination ( J:94884 )

• disorganized myelin sheaths with dilations suggesting degeneration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 2		DOID:0110726	OMIM:204500	J:94884

Genotype
MGI:3804729

ht4

• Allelic Composition: Tpp1^tm1Plob/Tpp1^tm1.1Plob
• Genetic Background: B6.129S1-Tpp1^tm1Plob/Tpp1^tm1.1Plob

mortality/aging

premature death ( J:136105 )

• median and maximal survival of 269 and 438 days

behavior/neurological

tremors ( J:136105 )

• onset of tremor occurs after 1 year of age

ataxia ( J:136105 )

• become increasingly ataxic

abnormal gait ( J:136105 )

• starting around 9 months of age, mutants develop an abnormal gait with a shortened stride and splaying of the rear limbs

• eventually develop a hunched appearance and a side-to-side sway as they walk

short stride length ( J:136105 )

nervous system

abnormal Purkinje cell morphology ( J:136105 )

• levels of the small proteolipid, subunit C of mitochondrial ATP synthase (SCMAS ), are slightly elevated in the Purkinje cell layer of the cerebellar cortex at 4 months of age

cellular

abnormal lysosome physiology ( J:136105 )

• later onset of neuronal ceroid lipofuscinosis disease and slower progression than in homozygous Tpp1^tm1Plob mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuronal ceroid lipofuscinosis 2		DOID:0110726	OMIM:204500	J:136105