Phenotypes associated with this allele

• Allele Symbol: Psen1^tm4.1Shn
• Allele Name: targeted mutation 4.1, Jie Shen
• Allele ID: MGI:5751732
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Psen1^tm4.1Shn/Psen1^tm4.1Shn	involves: 129 * C57BL/6 * C57BL/6J	MGI:5754378
cn2	Psen1^tm2Shn/Psen1^tm4.1Shn Psen2^tm1Haa/Psen2^tm1Haa Tg(Camk2a-cre)1Shn/0	involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6J * CBA	MGI:5754385
cx3	Psen1^tm4.1Shn/Psen1^+ Psen2^tm1Haa/Psen2^tm1Haa	involves: 129 * C57BL/6 * C57BL/6J	MGI:5754382
cx4	Psen1^tm4.1Shn/Psen1^+ Tg(PDGFB-APP)5Lms/0	involves: 129 * C57BL/6 * C57BL/6J * DBA/2	MGI:5754380
cx5	Psen1^tm4.1Shn/Psen1^+ Zbtb20^Tg(PDGFB-APPSwInd)20Lms/0	involves: 129 * C57BL/6 * C57BL/6J * DBA/2	MGI:5754381

Genotype
MGI:5754378

hm1

• Allelic Composition: Psen1^tm4.1Shn/Psen1^tm4.1Shn
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J

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

mortality/aging

perinatal lethality, complete penetrance ( J:219929 )

embryo

short rostral-caudal axis ( J:219929 )

limbs/digits/tail

short tail ( J:219929 )

kinked tail ( J:219929 )

nervous system

decreased cortical ventricular zone thickness ( J:219929 )

• thinning of the ventricular zone within the developing telencephalon at E16.5

• number of proliferating cells is reduced in the ventricular zone

abnormal lateral ganglionic eminence morphology ( J:219929 )

• thinning of the ventricular zone within the lateral ganglionic eminence at E16.5

Genotype
MGI:5754385

cn2

• Allelic Composition: Psen1^tm2Shn/Psen1^tm4.1Shn; Psen2^tm1Haa/Psen2^tm1Haa; Tg(Camk2a-cre)1Shn/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * C57BL/6J * CBA

nervous system

microgliosis ( J:219929 )

• in the neocortex and hippocampus

abnormal cerebral cortex morphology ( J:219929 )

• 31.5% reduction in cortical volume at 18 months of age

abnormal neocortex morphology ( J:219929 )

• increase in apoptosis in the neocortex

astrocytosis ( J:219929 )

• in the cortex

decreased neuron number ( J:219929 )

• 22.1% reduction in neuron number in the cerebral cortex at 18 months of age

neurodegeneration ( J:219929 )

• mice exhibit age-dependent neurodegeneration throughout the cerebral cortex

hematopoietic system

microgliosis ( J:219929 )

• in the neocortex and hippocampus

immune system

microgliosis ( J:219929 )

• in the neocortex and hippocampus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:219929

Genotype
MGI:5754382

cx3

• Allelic Composition: Psen1^tm4.1Shn/Psen1⁺; Psen2^tm1Haa/Psen2^tm1Haa
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J

behavior/neurological

abnormal spatial reference memory ( J:219929 )

• in the hidden-platform Morris water maze, mice exhibit higher latencies across the 14 day training period and show lower target quadrant occupancy in the probe test at day 7, indicating impaired reference memory acquisition

• although mice show similar target quadrant occupancies in the probe trial at da 13, they exhibit reduced target quadrant occupancy under partial-cue conditions in the probe trail at day 14, suggesting impaired hippocampal pattern completion

• in a spatial discrimination version of the radial arm maze task, mutants show more reference memory errors and a higher proportion of 45 degree turns into adjacent arms, indicating hippocampal spatial memory deficits

nervous system

impaired synaptic plasticity ( J:219929 )

• mice exhibit impaired short-term and long-term synaptic plasticity at hippocampal CA1 and CA3 synapses

reduced long-term potentiation ( J:219929 )

• long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses induced by pairing presynaptic stimuli with postsynaptic depolarization is reduced

• LTP is impaired at commissural/associational (C/a)-CA3 synapses

• however, NMDAR-mediated EPSCs are unaffected

increased synaptic depression ( J:219929 )

• short-term depression during the initial phase of the LTP-inducing stimulus train is increased at (C/A)-CA3 synapses

decreased paired-pulse facilitation ( J:219929 )

• mice show impaired short-term plasticity as indicated by reduced paired-pulse facilitation and frequency facilitation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:219929

Genotype
MGI:5754380

cx4

• Allelic Composition: Psen1^tm4.1Shn/Psen1⁺; Tg(PDGFB-APP)5Lms/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * DBA/2

nervous system

nervous system phenotype ( J:219929 )

N • no amyloid plaque deposition is seen in the cerebral cortex even at 18 months of age

Genotype
MGI:5754381

cx5

• Allelic Composition: Psen1^tm4.1Shn/Psen1⁺; Zbtb20^{Tg(PDGFB-APPSwInd)20Lms}/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * DBA/2

homeostasis/metabolism

amyloid beta deposits ( J:219929 )

• accelerated amyloid deposition in the cerebral cortex at 9 months of age compared to single Tg(PDGFB-APPSwInd)20Lms hemizygotes

nervous system

amyloid beta deposits ( J:219929 )

• accelerated amyloid deposition in the cerebral cortex at 9 months of age compared to single Tg(PDGFB-APPSwInd)20Lms hemizygotes