Tg(Prnp-MAPT*P301S)PS19Vle Transgene Detail MGI Mouse (MGI:3768407)

Tg(Prnp-MAPT*P301S)PS19Vle
Transgene Detail

Nomenclature

Symbol:	Tg(Prnp-MAPT*P301S)PS19Vle
Name:	transgene insertion PS19, Virginia M Y Lee
MGI ID:	MGI:3768407
Synonyms:	P301S tau (line PS19), PS19 Tg
Transgene:	Tg(Prnp-MAPT*P301S)PS19Vle Location: unknown

Transgene
origin

Strain of Origin:

(C57BL/6 x C3H)F1

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	The transgene construct contains the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter. The expression of the mutant human MAPT is 5-fold higher than the expression of the endogenous mouse Mapt protein. (J:119741)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 1 strain available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1	tg2
behavior/neurological		√	√
abnormal sexual interaction		√
abnormal eating behavior			√
limb grasping			√
weakness			√
hunched posture			√
paralysis			√
		tg1	tg2
life span/aging			√
premature death			√
		tg1	tg2
muscle			√
progressive muscle weakness			√
dystrophic muscle			√
		tg1	tg2
nervous system			√
abnormal brain morphology			√
abnormal brain ventricle morphology			√
abnormal amygdala morphology			√
abnormal entorhinal cortex morphology			√
abnormal hippocampus morphology			√
abnormal dentate gyrus morphology			√
abnormal hippocampal mossy fiber morphology			√
decreased pyramidal neuron number			√
hippocampal neuron degeneration			√
loss of hippocampal neurons			√
abnormal cerebral cortex morphology			√
neurofibrillary tangles			√
tau protein deposits			√
astrocytosis			√
abnormal spinal cord white matter morphology			√
abnormal CNS synaptic transmission			√
abnormal excitatory postsynaptic potential			√
reduced long term potentiation			√
decreased paired-pulse facilitation			√
neurodegeneration			√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype	Allelic Composition	Genetic Background
tg1	Tg(Prnp-MAPTP301S)PS19Vle/Tg(Prnp-MAPTP301S)PS19Vle	involves: C3H * C57BL/6
behavior/neurological abnormal sexual interaction (J:119741) homozygous females do not mate, so mice have to be maintained as hemizygotes
Genotype	Allelic Composition	Genetic Background
tg2	Tg(Prnp-MAPT*P301S)PS19Vle/0	involves: C3H * C57BL/6
life span/aging premature death (J:119741) ~80% of mice die by 12 months of age, with median survival of ~9 months behavior/neurological abnormal eating behavior (J:119741) mice are no longer able to feed after onset of paralysis limb grasping (J:119741) at 3 months of age, mice exhibit limb grasping and limb retraction when lifted by the tail, whereas mice expressing a wild-type MAPT transgene show no neurodegenerative phenotype up to 24 months of age weakness (J:119741) limb grasping at 3 months of age is followed by limb weakness hunched posture (J:119741) paralysis is associated with hunched-back posture paralysis (J:119741) mice show paralysis at 7-10 months of age nervous system abnormal brain morphology (J:119741) limb grasping at 3 months of age is followed by brain atrophy abnormal brain ventricle morphology (J:119741) by 8 months of age, ventricular dilatation is seen abnormal amygdala morphology (J:119741) neuron loss is observed at 12 months of age abnormal entorhinal cortex morphology (J:119741) neuron loss is observed at 12 months of age abnormal hippocampus morphology (J:119741) at 9 months of age, there is marked hippocampal atrophy, with ~25% and ~40% reductions in hippocampal volume at 9 and 12 months of age respectively abnormal dentate gyrus morphology (J:119741) at 3 months, mice have neurofilament light chain and tau-positive spheroids in the dentate gyrus, as well as in the cortex abnormal hippocampal mossy fiber morphology (J:119741) at 3 months but not at 6 months, neurofilament light chain-positive mossy fibers are not detected in CA3 of hippocampus at 3 months but not at 6 months, neurofilament light chain-positive mossy fibers are not detected in CA3 of hippocampus decreased pyramidal neuron number (J:119741) significant reduction in number is found at 12 months of age, but no loss is detected at 6 months hippocampal neuron degeneration (J:119741) loss of hippocampal neurons (J:119741) up to 6 months, mice show no neuron loss, but by 8 months of age, neuron loss in the hippocampus is seen, becoming more severe in hippocampus, as well as amygdala, neocortex and entorhinal cortex by 12 months of age abnormal cerebral cortex morphology (J:119741) at 3 months, mice have neurofilament light chain and tau-positive spheroids in the cerebral cortex prominent atrophy of neocortex is observed at 9 months of age, with a 20% reduction in volume at 12 months of age neurofibrillary tangles (J:119741) at 6 months of age, neurofibrillary tangles (NFT) are evident in neocortex, amygdala, hippocampus, brain stem and spinal cord but none are found in mice expressing wild-type human MAPT up to 24 months of age tau protein deposits (J:119741) with aging, brains of mice have increasing levels of insoluble tau deposits composed mainly of transgenic human tau; decrease in solubility of tau is observed between 3 and 6 months at 3 months of age, mutants and mice expressing wild-type transgenic human tau show weak perikaryal and dendritic tau staining mainly in hippocampus, amygdala, cortex, brain stem, and spinal cord; at 6 months, mutants show stronger tau-positive neuronal staining in the hippocampus, amygdala, and spinal cord but older mice expressing wild-type human tau protein show no increases up to 12 months astrocytosis (J:119741) microglial activation precedes astrogliosis in brain regions containing NFTs; this is found in the brain and spinal cord, especially in white matter at 3 months of age with increases seen at 6 months in white and gray matter of hippocampus, amygdala, entorhinal cortex and spinal cord gliosis is striking at 6 months in the white matter where little tau pathology exists younger mice (3-4 months) show no overt gliosis but increased microglial activation is detected in the hippocampus abnormal spinal cord white matter morphology (J:119741) at 3 months, mice have neurofilament light chain and tau-positive spheroids in the spinal cord white matter abnormal CNS synaptic transmission (J:119741) basal synaptic transmission is impaired at 6 months mice show small fiber volley amplitude, fEPSP slopes and amplitudes at all stimulus intensities tested abnormal excitatory postsynaptic potential (J:119741) at 6 months, the maximum fEPSP is reduced relative to wild-type MAPT transgenic mice reduced long term potentiation (J:119741) LTP in CA1 region of hippocampus is significantly deteriorated, indicating attenuated postsynaptic responsiveness and compromised synaptic plasticity, but at 6 months no overt reduction in neuron number is detected decreased paired-pulse facilitation (J:119741) at 6 months, mice show significantly reduce paired pulse facilitation (PPF) ratio at all stimulus intervals neurodegeneration (J:119741) mice show progressive neurodegeneration starting at 1 month of age, as determined by increasing loss of synaptophysin immunoreactivity muscle progressive muscle weakness (J:119741) mice show motor increasing weakness and neurogenic muscular atrophy after 3 months of age dystrophic muscle (J:119741) affected muscles show group atrophies with small angular fibers, indicating chronic denervation of motor neurons

References

Original:	J:119741 Yoshiyama Y et al., "Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model." Neuron 2007 Feb 1;53(3):337-51
All:	2 reference(s)

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