Phenotypes associated with this allele

• Allele Symbol: Tg(Camk2a-cre)T29-1Stl
• Allele Name: transgene insertion T29-1, Susumu Tonegawa
• Allele ID: MGI:2177650
• Summary: 22 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gria2^tm1.1Bvis/Gria2^tm1.1Bvis Tg(Camk2a-cre)T29-1Stl/0	129S6.Cg-Gria2^tm1.1Bvis Tg(Camk2a-cre)T29-1Stl	MGI:5694583
cn2	Itga3^tm1Rdav/Itga3^tm1Rdav Tg(Camk2a-cre)T29-1Stl/0	B6.Cg-Itga3^tm1Rdav Tg(Camk2a-cre)T29-1Stl	MGI:3843051
cn3	Gabrb3^tm2.1Geh/Gabrb3^tm2.1Geh Tg(Camk2a-cre)T29-1Stl/?	involves: 129 * BALB/c * C57BL/6 * SJL	MGI:3767262
cn4	Crebbp^tm1.2Ltz/Crebbp^tm1.2Ltz Tg(Camk2a-cre)T29-1Stl/0	involves: 129P2/OlaHsd * BALB/c * C57BL * C57BL/6J	MGI:4941348
cn5	Grin1^tm2Stl/Grin1^tm2Stl Tg(Camk2a-cre)T29-1Stl/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:3581524
cn6	Tsc2^tm1Djk/Tsc2^+ Atg7^tm1Tchi/Atg7^tm1Tchi Tg(Camk2a-cre)T29-1Stl/0	involves: 129S4/SvJae * BALB/c * C57BL * C57BL/6 * CBA/JNCrlj	MGI:5824126
cn7	Ckap5^tm1.1Eba/Ckap5^tm1.1Eba Tg(Camk2a-cre)T29-1Stl/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * BALB/c * C57BL * C57BL/6J	MGI:5570200
cn8	Nr3c1^tm2.1Ljm/Nr3c1^tm2.1Ljm Tg(Camk2a-cre)T29-1Stl/0	involves: 129S6/SvEvTac * BALB/c * C57BL	MGI:5803966
cn9	Arpc3^tm1Ssod/Arpc3^tm1Ssod Tg(Camk2a-cre)T29-1Stl/0	involves: 129S6/SvEvTac * BALB/c * C57BL	MGI:5509191
cn10	Grin2b^tm1.1Jlbr/Grin2b^tm1.1Jlbr Tg(Camk2a-cre)T29-1Stl/0	involves: 129S6/SvEvTac * BALB/c * C57BL/6	MGI:4443330
cn11	Anks1b^tm1Bnaj/Anks1b^tm1Bnaj Tg(Camk2a-cre)T29-1Stl/0	involves: 129S6/SvEvTac * BALB/c * C57BL * C57BL/6NTac	MGI:5779302
cn12	Lrp1^tm2Her/Lrp1^tm2Her Tg(Camk2a-cre)T29-1Stl/0	involves: 129S7/SvEvBrd * BALB/c * C57BL	MGI:4943741
cn13	Ssb^tm1Rjma/Ssb^tm2.1Rjma Tg(Camk2a-cre)T29-1Stl/0	involves: 129S/SvEv * BALB/c * C57BL * C57BL/6	MGI:5569497
cn14	Lgi1^tm2.1Jkc/Lgi1^tm2.1Jkc Tg(Camk2a-cre)T29-1Stl/0	involves: 129/Sv * BALB/cJ * C57BL/6	MGI:6275805
cn15	Phrf1^em1Mscha/Phrf1^em1Mscha Tg(Camk2a-cre)T29-1Stl/0	involves: BALB/c * C57BL	MGI:7549325
cn16	Tg(ACTB-MAP2K1*K97M)1Stl/0 Tg(Camk2a-cre)T29-1Stl/0	involves: BALB/c * C57BL/6	MGI:3707564
cn17	Drd1^tm2.1Stl/Drd1^tm2.1Stl Drd5^tm1.1Stl/Drd5^tm1.1Stl Tg(Camk2a-cre)T29-1Stl/0	involves: BALB/c * C57BL * C57BL/6	MGI:5603926
cn18	Atg7^tm1Tchi/Atg7^tm1Tchi Tg(Camk2a-cre)T29-1Stl/0	involves: BALB/c * C57BL * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj	MGI:5824124
cn19	Crbn^tm1.1Jjh/Crbn^tm1.1Jjh Tg(Camk2a-cre)T29-1Stl/0	involves: C57BL/6	MGI:5302203
cn20	Psen1^tm1Jzt/Psen1^tm1Jzt Psen2^tm1Ber/Psen2^tm1Ber Tg(Camk2a-cre)T29-1Stl/0	involves: C57BL/6 * CBA	MGI:3045186
cn21	Psen1^tm1Jzt/Psen1^tm1Jzt Tg(Camk2a-cre)T29-1Stl/0	involves: C57BL/6 * CBA	MGI:3045183
cn22	Grin1^tm2Stl/Grin1^tm2Stl Tg(Actb-tTA)1Jzt/0 Tg(Camk2a-cre)T29-1Stl/0 Tg(tetO-Grin1/GFP)1Jzt/0	involves: C57BL/6 * CBA	MGI:3038603

Genotype
MGI:5694583

cn1

• Allelic Composition: Gria2^tm1.1Bvis/Gria2^tm1.1Bvis; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: 129S6.Cg-Gria2^tm1.1Bvis Tg(Camk2a-cre)T29-1Stl

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

nervous system

enhanced long-term potentiation ( J:223717 )

• in CA1 after high frequency stimulation

• long term depression is unaffected

behavior/neurological

abnormal learning/memory/conditioning ( J:223717 )

• initial learning affected more than subsequent learning (NMDAR receptor vs NMDAR receptor independent)

impaired contextual conditioning behavior ( J:223717 )

• long term contextual fear conditioning is impaired

• dorsal hippocampal lesions also impair contextual fear conditioning

• pre-exposure to context fails to enhance fear conditioning

• short term memory remains intact

impaired spatial learning ( J:223717 )

• tested using a Morris water maze

abnormal long-term spatial reference memory ( J:223717 )

• impaired as tested using a radial maze

• spatial working memory not affected

Genotype
MGI:3843051

cn2

• Allelic Composition: Itga3^tm1Rdav/Itga3^tm1Rdav; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: B6.Cg-Itga3^tm1Rdav Tg(Camk2a-cre)T29-1Stl

behavior/neurological

impaired spatial working memory ( J:147820 )

• in a nonmatch-to-place T-maze assay, mice exhibit impaired working memory following a 20 second delay between trials

• however, mice trained in a Morris water maze perform normally

nervous system

reduced long-term potentiation ( J:147820 )

• N-methyl-D-aspartic acid receptor-dependent long term potentiation (LTP) is severely impaired compared to in wild-type mice

• however, glutamate receptor-dependent and high frequency-stimulated LTP are normal

Genotype
MGI:3767262

cn3

• Allelic Composition: Gabrb3^tm2.1Geh/Gabrb3^tm2.1Geh; Tg(Camk2a-cre)T29-1Stl/?
• Genetic Background: involves: 129 * BALB/c * C57BL/6 * SJL

mortality/aging

postnatal lethality, incomplete penetrance ( J:127877 )

• born at expected Mendelian frequency

• no cleft palate found

• about 30% die between 15 and 25 days after birth

• 72% of mice that died prematurely were male

behavior/neurological

abnormal behavior ( J:127877 )

• hyperresponsive to human contact

impaired behavioral response to xenobiotic ( J:127877 )

• less sensitive to the sedative/hypnotic effects of etomidate

increased food intake ( J:127877 )

• average food consumption was greater in mutant over control

hyperactivity ( J:127877 )

• the greater total activity in home cage

abnormal maternal nurturing ( J:127877 )

♀ • failed to care for pups

reduced male mating frequency ( J:127877 )

♂ • did not produce copulation plug when mated with superovulated females

absence seizures ( J:127877 )

• appeared to be "frozen" in their home cage

nervous system

absence seizures ( J:127877 )

• appeared to be "frozen" in their home cage

reproductive system

reduced female fertility ( J:127877 )

♀ • four out of six female either did not produce any offspring or produced letters infrequently

reduced male fertility ( J:127877 )

♂ • reduced number of mating

growth/size/body

obese ( J:127877 )

• some mutant adult mice became obese

Genotype
MGI:4941348

cn4

• Allelic Composition: Crebbp^tm1.2Ltz/Crebbp^tm1.2Ltz; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129P2/OlaHsd * BALB/c * C57BL * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:168984 )

N • mice exhibit normal anxiety levels, fear conditioning, and spatial navigation

abnormal behavior ( J:168984 )

• after 3 consecutive days in the same arena, mice exhibit slightly less locomotor habituation compared with wild-type mice

impaired long-term object recognition memory ( J:168984 )

• mice exhibit impaired long term recognition memory compared with wild-type mice

nervous system

nervous system phenotype ( J:168984 )

N • neuronal viability is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Rubinstein-Taybi syndrome		DOID:1933	OMIM:180849 OMIM:610543 OMIM:613684	J:168984

Genotype
MGI:3581524

cn5

• Allelic Composition: Grin1^tm2Stl/Grin1^tm2Stl; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

behavior/neurological

abnormal contextual conditioning behavior ( J:60730 )

• impaired hippocampus-dependent, but not hippocampus-independent, fear memory that can be rescued with enriched training

abnormal olfactory discrimination memory ( J:60730 )

• impaired olfactory-discrimination memory that can be rescued with enriched training

impaired social transmission of food preference ( J:60730 )

abnormal object recognition memory ( J:60730 )

• deficit in novel object recognition memory that can be partially rescued with enriched training

abnormal spatial learning ( J:37457 )

• impaired spatial memory in the hidden-platform Morris water maze test, with some progressive improvement in escape latencies but unimpaired nonspatial learning

nervous system

abnormal excitatory postsynaptic currents ( J:37457 )

• lack the slow component of the excitatory postsynaptic current mediated by NMDA receptors

absence of NMDA-mediated synaptic currents ( J:37457 )

• lack the slow component of the excitatory postsynaptic current mediated by NMDA receptors, however postsynaptic AMPA receptors as well as presynaptic terminals operate normally

reduced long-term potentiation ( J:37457 )

• lack long term potentiation in the CA1 synapses

Genotype
MGI:5824126

cn6

• Allelic Composition: Tsc2^tm1Djk/Tsc2⁺; Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL * C57BL/6 * CBA/JNCrlj

behavior/neurological

abnormal social investigation ( J:217829 )

• in the three-chamber test, mice show impaired preference for sniffing the social target and for social novelty

abnormal response to social novelty ( J:217829 )

• during dyadic encounters, mice spend less time sniffing stimulus mice than control littermates

cellular

abnormal autophagy ( J:217829 )

• mice exhibit high levels of p62/ubiquitin-positive aggregates in cortices at P30, indicating loss of autophagy

nervous system

abnormal dendritic spine morphology ( J:217829 )

• between P21 and P29, basal dendrites from layer V A1/S2 pyramidal neurons exhibit more spines than controls, indicating impaired spine pruning, with only 2% of spines pruned

• treatment with rapamycin does not rescue spine pruning

homeostasis/metabolism

abnormal autophagy ( J:217829 )

• mice exhibit high levels of p62/ubiquitin-positive aggregates in cortices at P30, indicating loss of autophagy

Genotype
MGI:5570200

cn7

• Allelic Composition: Ckap5^tm1.1Eba/Ckap5^tm1.1Eba; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * BALB/c * C57BL * C57BL/6J

behavior/neurological

behavior/neurological phenotype ( J:205779 )

N • mice exhibit normal balance, coordination and endurance on a rotarod, gait, anxiety in the elevated zero maze, and passive avoidance

abnormal habituation to a new environment ( J:205779 )

• mutants exhibit almost twice as much activity over a one hour time period than controls in the open field test, however, when activity is recorded over 5 minute intervals, controls show a decrease in activity over time that is not seen in mutants, indicating that mutants have impaired short term habituation to spatial stimuli

decreased anxiety-related response ( J:205779 )

• mutants exhibit a decrease in marble burying, burying few if any marbles compared to controls which bury 30% of marbles

hyperactivity ( J:205779 )

• mutants exhibit almost twice as much activity over a one hour time period than controls in the open field test

abnormal vocalization ( J:205779 )

♂ • mutant males exhibit a higher proportion of high frequency of ultrasonic vocalizations (USVs) compared to controls which show a higher proportion of low frequency USVs

♂ • increase in vocalization and an increase in high frequency USVs indicates altered response to sexual or pheromonal olfactory stimuli

excessive vocalization ( J:205779 )

♂ • mutant males placed next to a female mouse vocalize more than controls

nervous system

abnormal brain morphology ( J:205779 )

• mice older than 4 months of age exhibit late onset morphological changes outside the CA1 region of the hippocampus and behavioral defects

abnormal hippocampus pyramidal cell layer ( J:205779 )

• decrease (less than 20%) in the thickness of the CA1 stratum pyramidale in mutants older than 45 days

abnormal hippocampus pyramidal cell morphology ( J:205779 )

• spine density in apical dendrites of CA1 pyramidal neurons is about 70% of control in mice younger than 3 months of age

abnormal dendritic spine morphology ( J:205779 )

• spine density in apical dendrites of CA1 pyramidal neurons is about 70% of control in mice younger than 3 months of age

abnormal neuron physiology ( J:205779 )

• reduction in granule assembly and translation of granule RNAs in cultured hippocampal neurons

abnormal excitatory postsynaptic potential ( J:205779 )

• input-out curves of field excitatory postsynaptic potentials from the CA1 region of the stratum radiatum in hippocampal slices evoked by stimulation of Schaffer collateral axons show reduced amplitudes and slopes, indicating reduced basal excitatory transmission

• field responses in the presence of GABAzine, a GABA antagonist, are smaller in mutants than in controls

reduced long-term potentiation ( J:205779 )

• short-term potentiation in evoked field potentials is normal, but mutants are unable to maintain LTP of evoked potentials

Genotype
MGI:5803966

cn8

• Allelic Composition: Nr3c1^tm2.1Ljm/Nr3c1^tm2.1Ljm; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL

nervous system

nervous system phenotype ( J:197150 )

N • as in wild-type mice, prior treatment with glucocorticoid stress hormone followed by middle cerebral artery occlusion sensitizes neurons to excityotoxicity

abnormal response to CNS ischemic injury ( J:197150 )

• prior treatment with glucocorticoid stress hormone fail to exhibit a reduction in numbers of infiltrating monocytes after middle cerebral artery occlusion unlike in wild-type mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:197150 )

N • as in wild-type mice, prior treatment with glucocorticoid stress hormone followed by middle cerebral artery occlusion sensitizes neurons to excityotoxicity

abnormal response to CNS ischemic injury ( J:197150 )

• prior treatment with glucocorticoid stress hormone fail to exhibit a reduction in numbers of infiltrating monocytes after middle cerebral artery occlusion unlike in wild-type mice

Genotype
MGI:5509191

cn9

• Allelic Composition: Arpc3^tm1Ssod/Arpc3^tm1Ssod; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL

behavior/neurological

behavior/neurological phenotype ( J:196577 )

N • mice exhibit normal basal startle responses

abnormal object recognition memory ( J:196577 )

• in a novel object recognition test, adolescent and adult mice exhibit disrupted episodic learning and memory compared with control mice

• early and pronounced deficit in short-term, long-term and remote memory in a novel object recognition test

impaired long-term object recognition memory ( J:196577 )

• impaired in adolescent and adult mice in a novel object recognition test

impaired short-term object recognition memory ( J:196577 )

• impaired in adolescent and adult mice in a novel object recognition test

abnormal spatial working memory ( J:196577 )

• impaired in adult, but not adolescent, mice in a Y-maze

hyperactivity ( J:196577 )

• adult, but not adolescent, mice in the home cage

increased vertical activity ( J:196577 )

• in adult, but not adolescent, mice

increased stereotypic behavior ( J:196577 )

• in adult, but not adolescent, mice

abnormal social/conspecific interaction behavior ( J:196577 )

• reduced social interaction of in adult, but not adolescent, mice

nervous system

abnormal dendritic spine morphology ( J:196577 )

• progressive loss of spine at P120

• neurons exhibit a decreased fraction of mushroom type spines and increased filopodia-like spines compared with control neurons

abnormal synapse morphology ( J:196577 )

• at 4 months, mice exhibit a loss of synapses onto spines in the stratum radiatum of the hippocampus and cerebral cortex compared with control mice

decreased prepulse inhibition ( J:196577 )

• in adolescent and adult mice

Genotype
MGI:4443330

cn10

• Allelic Composition: Grin2b^tm1.1Jlbr/Grin2b^tm1.1Jlbr; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6

nervous system

decreased dendritic spine density ( J:159387 )

• CA1 pyramidal neurons exhibit lower spine density of dendrites compared to in wild-type mice

abnormal excitatory postsynaptic currents ( J:159387 )

• unlike in wild-type mice, Ro 25-6981 fails to inhibit eEPSC

decreased excitatory postsynaptic current amplitude ( J:159387 )

• NMDAR-eEPSC amplitude is slightly reduced compared to in wild-type mice

short excitatory postsynaptic current decay time ( J:159387 )

• NMDAR-evoked excitatory postsynaptic current (eEPSC) decay time constants are almost twice as fast as in wild-type mice

abnormal excitatory postsynaptic potential ( J:159387 )

• unlike in wild-type mice, no increase in field excitatory postsynaptic potential (fEPSP) is observed under a protocol designed to evoke modest, subsaturating long term potentiation

• under a protocol designed to produce saturating long term potentiation, mice fail to exhibit a decrease in fEPSP during the first time point compared with similarly treated wild-type mice

• under a long term depression protocol, fEPSP slopes fail to decrease as in similarly treated wild-type mice

• under a long term depression protocol with DL-AP-5 co-application with glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC), mice exhibit an increase in the fEPSC slope unlike in wild-type mice and an AP-5 washout with another round of stimulation does not produce a lasting decrease in fEPSP slope as observed in similarly treated wild-type mice

reduced long-term potentiation ( J:159387 )

• unlike in wild-type mice, no increase in field excitatory postsynaptic potential (fEPSP) is observed under a protocol designed to evoke modest, subsaturating long term potentiation

• under a protocol designed to produce saturating long term potentiation, mice fail to exhibit a decrease in fEPSP during the first time point compared with similarly treated wild-type mice

absent long-term depression ( J:159387 )

• application of the glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC) does not produce long term depression unlike in wild-type mice

reduced long-term depression ( J:159387 )

• under a long term depression protocol, fEPSP slopes fail to decrease as in similarly treated wild-type mice

• under a long term depression protocol with DL-AP-5 co-application with glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC), mice exhibit an increase in the fEPSC slope unlike in wild-type mice and an AP-5 washout with another round of stimulation does not produce a lasting decrease in fEPSP slope as observed in similarly treated wild-type mice

behavior/neurological

abnormal learning/memory/conditioning ( J:159387 )

• in a T maze, mice exhibit fewer spontaneous alternations compared with wild-type mice

abnormal associative learning ( J:159387 )

• mice exhibit less freezing during retrieval of a trace-conditioned fear memory compared with similarly treated wild-type mice

• however, mice exhibit normal delay-conditioned fear memory and freezing during conditioning of before tone presentation

abnormal spatial learning ( J:159387 )

• in a hidden platform Morris water maze, mice exhibit a longer latency in finding a hidden platform and spend less time in a platform quadrant compared with wild-type mice

• however, mice exhibit normal performance during visible platform training

increased thigmotaxis ( J:159387 )

• in a hidden platform Morris water maze but not when the platform is visible

impaired swimming ( J:159387 )

• in a hidden platform Morris water maze, mice swim slower than wild-type mice

• however, swimming is normal when the platform is visible

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:159387 )

• unlike in wild-type mice, Ro 25-6981 fails to inhibit evoked excitatory postsynaptic current (eEPSC)

• under a long term depression protocol with DL-AP-5 co-application with glutamate transporter inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (tPDC), mice exhibit an increase in the fEPSC slope unlike in wild-type mice and an AP-5 washout with another round of stimulation does not produce a lasting decrease in fEPSP slope as observed in similarly treated wild-type mice

• application of tPDC does not produce long term depression unlike in wild-type mice

• however, DL-AP-5 inhibits eEPSP as in wild-type mice

Genotype
MGI:5779302

cn11

• Allelic Composition: Anks1b^tm1Bnaj/Anks1b^tm1Bnaj; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL * C57BL/6NTac

nervous system

nervous system phenotype ( J:222552 )

N • CA1 pyramidal cell synapses exhibit normal input-output function with normal amplitudes or frequencies of AMPAR-mediated miniature excitatory postsynaptic currents

impaired synaptic plasticity ( J:222552 )

• impaired NMDAR-dependent synaptic plasticity at hippocampal Sch-CA1 synapses

short excitatory postsynaptic current decay time ( J:222552 )

• faster decay of NMDAR-mediated excitatory postsynaptic currents

• reduced sensitivity to Ro25-6981 but increased sensitivity to low doses of zinc, which selectively blocks GluN2B-containing and GluN2A-containing NMDARs

reduced long-term depression ( J:222552 )

• reduced NMDAR-dependent long term depression

• however, mGluR(Grm8)-dependent LTD is not affected

Genotype
MGI:4943741

cn12

• Allelic Composition: Lrp1^tm2Her/Lrp1^tm2Her; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c * C57BL

nervous system

decreased brain cholesterol level ( J:167724 )

• in the cortex of the brain at 12 months of age

decreased dendritic spine density ( J:167724 )

• decrease in spine densities of apical oblique and basal shaft dendrites of pyramidal neurons in the cortex and in the CA1 region of the hippocampus at 18 months but not at 12 months of age

abnormal synapse morphology ( J:167724 )

• expression analysis indicates an age dependent decrease in synaptic density

neurodegeneration ( J:167724 )

• significant increase in apoptotic cells in the cortex and hippocampus at 24 months but not at 18 months of age

abnormal nervous system physiology ( J:167724 )

• significantly lower levels of sulfatide, galactosylceramide, cholesterol and triglyceride in the cortex of the brain at 12 months of age

• amyloid-beta levels are decreased in the hippocampus at 18 months of age, indicating that the neurodegeneration likely occurs by an amyloid-beta independent mechanism

brain inflammation ( J:167724 )

• increase in reactive astrocytes and microglial activation in the CA1 region of the hippocampus and in the dentate gyrus but not in the CA3 region of the hippocampus at 18 months of age

reduced long-term potentiation ( J:167724 )

• severely reduced in hippocampal slices at 18 months of age

behavior/neurological

abnormal associative learning ( J:167724 )

impaired contextual conditioning behavior ( J:167724 )

• exhibit significantly less freezing time than controls at 18 months of age

impaired cued conditioning behavior ( J:167724 )

• exhibit significantly less freezing time than controls at 18 months of age

abnormal motor capabilities/coordination/movement ( J:167724 )

limb grasping ( J:167724 )

• develops by 13 months of age

impaired coordination ( J:167724 )

• at 18 months of age

hyperactivity ( J:167724 )

• in an open field test at 18 months of age

homeostasis/metabolism

abnormal lipid level ( J:167724 )

• significantly lower levels of sulfatide and galactosylceramide in the cortex of the brain at 12 months of age

decreased brain cholesterol level ( J:167724 )

• in the cortex of the brain at 12 months of age

decreased triglyceride level ( J:167724 )

• in the cortex of the brain at 12 months of age

immune system

brain inflammation ( J:167724 )

• increase in reactive astrocytes and microglial activation in the CA1 region of the hippocampus and in the dentate gyrus but not in the CA3 region of the hippocampus at 18 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:167724

Genotype
MGI:5569497

cn13

• Allelic Composition: Ssb^tm1Rjma/Ssb^tm2.1Rjma; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129S/SvEv * BALB/c * C57BL * C57BL/6

nervous system

decreased brain weight ( J:207687 )

• after 5 weeks

• rapid decline from 13 to 25 weeks, slowed decline afterward

• at 59 to 79 weeks

decreased forebrain size ( J:207687 )

• postnatal loss of forebrain mass at 16 and 32 weeks

forebrain hypoplasia ( J:207687 )

• progressive cell loss

abnormal cerebral cortex morphology ( J:207687 )

• loss of cortical cytoarchitecture at 16 and 32 weeks

thin cerebral cortex ( J:207687 )

• progressive neurodegeneration in the cerebral cortex (starting at 16 weeks) and hippocampus starting

• severely diminished at 65 weeks

abnormal neuron morphology ( J:207687 )

• decrease in neuronal density at 16 and 32 weeks

hippocampus pyramidal cell degeneration ( J:207687 )

• in the CA1 and subiculum

• however, the CA3 and dentate gyrus are relatively spared

neurodegeneration ( J:207687 )

• progressive neurodegeneration in the cerebral cortex and hippocampus

Genotype
MGI:6275805

cn14

• Allelic Composition: Lgi1^tm2.1Jkc/Lgi1^tm2.1Jkc; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: 129/Sv * BALB/cJ * C57BL/6

nervous system

nervous system phenotype ( J:269784 )

N • mice do not develop seizures, cortical dysplasia or hypercellularity in the outer cortical layers

Genotype
MGI:7549325

cn15

• Allelic Composition: Phrf1^em1Mscha/Phrf1^em1Mscha; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: BALB/c * C57BL

nervous system

nervous system phenotype ( J:294183 )

N • mice exhibit normal paired-pulse facilitation and long-term potentiation

abnormal Purkinje cell dendrite morphology ( J:294183 )

• reduced dendritic complexity, decreased dendritic branches, and reduced internodal segment length of CA1 pyramidal neurons

impaired synaptic plasticity ( J:294183 )

• after TGF-beta1 treatment

behavior/neurological

impaired spatial learning ( J:294183 )

• reduced spontaneous alternations in a Y-maze

abnormal spatial working memory ( J:294183 )

• in a Morris water maze

increased anxiety-related response ( J:294183 )

• in an open field, mice spend more time on the peripheral and less in the central areas compared with control mice

• in an elevated-plus maze, mice spend more time in the closed arm and less time in the open arm compared with control mice

• in a light/dark box, mice spend less time in the light area compared with control mice

increased thigmotaxis ( J:294183 )

• in an open field

abnormal response to novel object ( J:294183 )

• mice spend more time exploring a novel object than a familiar one compared with control mice

Genotype
MGI:3707564

cn16

• Allelic Composition: Tg(ACTB-MAP2K1*K97M)1Stl/0; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: BALB/c * C57BL/6

behavior/neurological

abnormal contextual conditioning behavior ( J:88546 )

• when tested for retention 24 hours after contextual fear conditioning, mutants show reduced levels of freezing relative to wild-type (mutant - 36.6% vs wild-type - 57.5%)

abnormal cued conditioning behavior ( J:88546 )

• 48 hours after a cued fear conditioning test, where a tone was the conditioned stimulus, mutants show a low level of freezing prior to tone presentation, indicating impairment of contextual memory

abnormal spatial learning ( J:88546 )

• in the Morris water maze test, mutants showed a tendency toward longer escape latencies compared to wild-type

• in probe trials with the platform hidden, mutant mice spend less time searching the target quadrant, and show less accurate identification of the precise platform location by having a reduced number of platform crossings

nervous system

abnormal excitatory postsynaptic potential ( J:88546 )

• field EPSPs in mutant hippocampal slice preparations return to levels near unstimulated levels by 3 hours posttetaniziation, while in control slices the fEPSPs (ie. late LTP remains elevated

abnormal long-term potentiation ( J:88546 )

• application of 4 trains of tetanic stimulation at 5 minute intervals, elicits long-lasting (>3 hours) potentiation in control hippocampal slices, but in mutants potentiation is unstable and decays progressively

• mutants display selective impairment in translational component of late-LTP (L-LTP); the defect is transcription-independent, translation-dependent, as shown by difference in inhibition kinetics of actinomycin-D (transcriptional inhibitor) and anisomycin (translational inhibitor)

homeostasis/metabolism

abnormal enzyme/coenzyme activity ( J:88546 )

• ERK activation in the forebrain is inhibited, causing selective deficits in hippocampal memory retention and translation-dependent phase of late-LTP

Genotype
MGI:5603926

cn17

• Allelic Composition: Drd1^tm2.1Stl/Drd1^tm2.1Stl; Drd5^tm1.1Stl/Drd5^tm1.1Stl; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: BALB/c * C57BL * C57BL/6

behavior/neurological

impaired contextual conditioning behavior ( J:211355 )

• mice exhibit deficits in contextual fear conditioning

• mice exhibit reduced freezing levels in 24 hour fear memory test, however, conditioning to tone is normal in an amygdala-dependent cued-fear conditioning protocol

decreased fear-related response ( J:211355 )

nervous system

abnormal long-term potentiation ( J:211355 )

• impaired late phase long term potentiation (L-LTP) at the medial perforant path-dentate gyrus synapse

• mice exhibit a reduced fEPSP (excitatory postsynaptic potential) slope following a theta burst used to induce L-LTP as compared to controls

Genotype
MGI:5824124

cn18

• Allelic Composition: Atg7^tm1Tchi/Atg7^tm1Tchi; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: BALB/c * C57BL * C57BL/6J * C57BL/6NCrlj * CBA/JNCrlj

behavior/neurological

abnormal social investigation ( J:217829 )

• in the three-chamber test, mice show impaired preference for sniffing the social target and for social novelty

• however, mice do not exhibit repetitive behaviors, motor defects, or anxiety-like behaviors

• treatment with rapamycin does not rescue social deficits

abnormal response to social novelty ( J:217829 )

• during dyadic encounters, mice spend less time sniffing stimulus mice than control littermates

homeostasis/metabolism

impaired autophagy ( J:217829 )

• mice exhibit occasional p62/ubiquitin-positive inclusions in pyramidal neurons at P20 and prominent p62/ubiquitin-positive aggregates in layer II-III and layer V-VI pyramidal neurons at P30, indicating loss of autophagy between P20 and P30 in cortical pyramidal neurons

cellular

impaired autophagy ( J:217829 )

• mice exhibit occasional p62/ubiquitin-positive inclusions in pyramidal neurons at P20 and prominent p62/ubiquitin-positive aggregates in layer II-III and layer V-VI pyramidal neurons at P30, indicating loss of autophagy between P20 and P30 in cortical pyramidal neurons

nervous system

abnormal dendritic spine morphology ( J:217829 )

• by P29-P30, but not at P19-P20, basal dendrites from layer V A1/S2 pyramidal neurons exhibit more spines than controls, indicating impaired spine pruning, with only 3% of spines pruned between P21 and P29

• treatment with rapamycin does not rescue spine pruning

Genotype
MGI:5302203

cn19

• Allelic Composition: Crbn^tm1.1Jjh/Crbn^tm1.1Jjh; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:179427 )

N • mice exhibit normal basal locomotion and anxiety-like behaviors

impaired contextual conditioning behavior ( J:179427 )

• mice freeze significantly less than control mice in a contextual fear conditioning task, indicating deficit it associative learning

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive intellectual developmental disorder		DOID:0060308	OMIM:PS249500	J:179427

Genotype
MGI:3045186

cn20

• Allelic Composition: Psen1^tm1Jzt/Psen1^tm1Jzt; Psen2^tm1Ber/Psen2^tm1Ber; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: C57BL/6 * CBA

behavior/neurological

abnormal object recognition memory ( J:90685 )

• by 10 months of age mutants have impaired performance in a novel object recognition test

hyperactivity ( J:90685 )

• by 10 months of age some mutants show increased activity in an open field test

cellular

abnormal apoptosis ( J:90685 )

• a dramatic increase in apoptosis is seen in the degenerating forebrain

growth/size/body

weight loss ( J:90685 )

• by 10 months of age mutant mice start to show reduced body weights compared to wild-type

nervous system

enlarged lateral ventricles ( J:90685 )

• the lateral ventricles are immensely enlarged compared to wild-type or single knockout mice

enlarged third ventricle ( J:90685 )

• the third ventricle is immensely enlarged compared to wild-type or single knockout mice

abnormal corpus callosum morphology ( J:90685 )

• the thickness of the corpus callosum is about a third that of controls

abnormal hippocampus molecular cell layer ( J:90685 )

• the thickness of the molecular layers between the CA1 pyramidal cells and dentate gyrus is significantly reduced

abnormal cerebral cortex morphology ( J:90685 )

• the cortex is about half the normal thickness and the 6 layers can no longer be distinguished

gliosis ( J:90685 )

• increased Gfap expression indicates that reactive astrogliosis occurs along with forebrain degeneration

abnormal neuron morphology ( J:90685 )

• changes in the expression of several markers indicate that neuronal atrophy occurs along with forebrain degeneration

neurodegeneration ( J:90685 )

• degeneration is seen in the forebrain

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:90685
Alzheimer's disease 4		DOID:0110040	OMIM:606889	J:90685

Genotype
MGI:3045183

cn21

• Allelic Composition: Psen1^tm1Jzt/Psen1^tm1Jzt; Tg(Camk2a-cre)T29-1Stl/0
• Genetic Background: involves: C57BL/6 * CBA

behavior/neurological

abnormal contextual conditioning behavior ( J:73252 )

• exposure to environmental enrichment following contextual fear conditioning results in a significant increase in freezing responses during retention tests

cellular

decreased cell proliferation ( J:73252 )

• environmental enrichment induces significantly less neurogenesis in the dentate gyrus of the brain in mutants compared to wild-type controls

nervous system

abnormal dentate gyrus morphology ( J:73252 )

• following environmental enrichment the number of newborn neurons in the subgranular zone and molecular layer of the dentate gyrus are 39% and 48% less respectively compared to wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:73252

Genotype
MGI:3038603

cn22

• Allelic Composition: Grin1^tm2Stl/Grin1^tm2Stl; Tg(Actb-tTA)1Jzt/0; Tg(Camk2a-cre)T29-1Stl/0; Tg(tetO-Grin1/GFP)1Jzt/0
• Genetic Background: involves: C57BL/6 * CBA

behavior/neurological

abnormal learning/memory/conditioning ( J:77659 )

• deficits in learning, memory and conditioning are seen in doxycycline treated mutants where expression of Grin1 is knocked out and expression of Grin1-GFP in the CA1 region of the hippocampus is blocked but deficits in learning, memory and conditioning are not seen in untreated mutants

abnormal contextual conditioning behavior ( J:77659 , J:88689 )

• with doxycycline treatment prior to or immediately after training mutants show significantly fewer freezing responses compared to untreated mutants in a retention test following a fear-conditioning task (J:77659)

• with doxycycline treatment just prior to testing (investigating the role of Grin1 in memory retrieval) no significant difference in a 1-month retention test following a fear-conditioning task is seen (J:77659)

• no difference in cued-fear conditioning behavior is seen with doxycycline treatment (J:77659)

• with doxycycline treatment for 30 days in the seventh month after training mutants show severe deficits in retention of remote contextual fear memory in a 9-month contextual retention test (J:88689)

• no deficit was seen with doxycycline treatment for 7 days in the seventh month after training (J:88689)

• no difference in cued-fear conditioning behavior is seen with doxycycline treatment (J:88689)

• 2 months after stopping doxycycline treatment mutants perform normally in 1-day contextual fear retention, visual memory, open field behavior and rotorod tests (J:88689)

abnormal spatial learning ( J:77659 )

• with doxycycline treatment prior to or immediately after training mutants exhibited longer escape latency in a hidden-platform water maze compared to untreated mutants

• with doxycycline treatment just prior to testing (investigating the role of Grin1 in memory retrieval) no significant difference in escape latency is seen

• deficits in spatial learning and memory are also seen in mutants with doxycycline treatment prior to testing in the transfer test compared to untreated mutants

nervous system

absence of NMDA-mediated synaptic currents ( J:77659 , J:88689 )

• with doxycycline treatment excitation postsynaptic potentials are absent in the CA1 hippocampal region (J:77659)

• no long-term potentiation is observed in doxycycline treated homozygotes (J:77659)

• with a 5 day doxycycline treatment no long-term potentiation is observed in mutants (J:88689)