Mouse Genome Informatics
cn1
    Itga3tm1Rdav/Itga3tm1Rdav
Tg(Camk2a-cre)T29-1Stl/0

B6.Cg-Itga3tm1Rdav Tg(Camk2a-cre)T29-1Stl
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 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


Mouse Genome Informatics
cn2
    Gabrb3tm2.1Geh/Gabrb3tm2.1Geh
Tg(Camk2a-cre)T29-1Stl/?

involves: 129 * BALB/c * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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
• hyperresponsive to human contact
• less sensitive to the sedative/hypnotic effects of etomidate
• average food consumption was greater in mutant over control
• the greater total activity in home cage
• failed to care for pups (J:127877)
• did not produce copulation plug when mated with superovulated females (J:127877)
• appeared to be "frozen" in their home cage

nervous system
• appeared to be "frozen" in their home cage

reproductive system
• four out of six female either did not produce any offspring or produced letters infrequently (J:127877)
• reduced number of mating (J:127877)

growth/size/body
• some mutant adult mice became obese


Mouse Genome Informatics
cn3
    Crebbptm1.2Ltz/Crebbptm1.2Ltz
Tg(Camk2a-cre)T29-1Stl/0

involves: 129P2/OlaHsd * BALB/c * C57BL * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit normal anxiety levels, fear conditioning, and spatial navigation (J:168984)
• after 3 consecutive days in the same arena, mice exhibit slightly less locomotor habituation compared with wild-type mice
• mice exhibit impaired long term recognition memory compared with wild-type mice

nervous system
N
• neuronal viability is normal (J:168984)

Mouse Models of Human Disease
OMIM IDRef(s)
Rubinstein-Taybi Syndrome 1; RSTS1 180849 J:168984


Mouse Genome Informatics
cn4
    Ssbtm1Rjma/Ssbtm2.1Rjma
Tg(Camk2a-cre)T29-1Stl/0

involves: 129S/SvEv * BALB/c * C57BL * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• after 5 weeks
• rapid decline from 13 to 25 weeks, slowed decline afterward
• at 59 to 79 weeks
• postnatal loss of forebrain mass at 16 and 32 weeks
• progressive cell loss
• loss of cortical cytoarchitecture at 16 and 32 weeks
• progressive neurodegeneration in the cerebral cortex (starting at 16 weeks) and hippocampus starting
• severely diminished at 65 weeks
• decrease in neuronal density at 16 and 32 weeks
• in the CA1 and subiculum
• however, the CA3 and dentate gyrus are relatively spared
• progressive neurodegeneration in the cerebral cortex and hippocampus


Mouse Genome Informatics
cn5
    Grin1tm2Stl/Grin1tm2Stl
Tg(Camk2a-cre)T29-1Stl/0

involves: 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• impaired hippocampus-dependent, but not hippocampus-independent, fear memory that can be rescued with enriched training
• impaired olfactory-discrimination memory that can be rescued with enriched training
• deficit in novel object recognition memory that can be partially rescued with enriched training
• impaired spatial memory in the hidden-platform Morris water maze test, with some progressive improvement in escape latencies but unimpaired nonspatial learning

nervous system
• lack the slow component of the excitatory postsynaptic current mediated by NMDA receptors
• lack the slow component of the excitatory postsynaptic current mediated by NMDA receptors, however postsynaptic AMPA receptors as well as presynaptic terminals operate normally
• lack long term potentiation in the CA1 synapses


Mouse Genome Informatics
cn6
    Ckap5tm1.1Eba/Ckap5tm1.1Eba
Tg(Camk2a-cre)T29-1Stl/0

involves: 129S4/SvJaeSor * 129S6/SvEvTac * BALB/c * C57BL * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit a decrease in marble burying, burying few if any marbles compared to controls which bury 30% of marbles
• however, mice exhibit normal balance, coordination and endurance on a rotarod, gait, anxiety in the elevated zero maze, and passive avoidance
• 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
• mutants exhibit almost twice as much activity over a one hour time period than controls in the open field test
• 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 (J:205779)
• increase in vocalization and an increase in high frequency USVs indicates altered response to sexual or pheromonal olfactory stimuli (J:205779)
• mutant males placed next to a female mouse vocalize more than controls (J:205779)

nervous system
• mice older than 4 months of age exhibit late onset morphological changes outside the CA1 region of the hippocampus and behavioral defects
• decrease (less than 20%) in the thickness of the CA1 stratum pyramidale in mutants older than 45 days
• spine density in apical dendrites of CA1 pyramidal neurons is about 70% of control in mice younger than 3 months of age
• spine density in apical dendrites of CA1 pyramidal neurons is about 70% of control in mice younger than 3 months of age
• reduction in granule assembly and translation of granule RNAs in cultured hippocampal neurons
• 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
• short-term potentiation in evoked field potentials is normal, but mutants are unable to maintain LTP of evoked potentials


Mouse Genome Informatics
cn7
    Grin2btm1.1Jlbr/Grin2btm1.1Jlbr
Tg(Camk2a-cre)T29-1Stl/0

involves: 129S6/SvEvTac * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• CA1 pyramidal neurons exhibit lower spine density of dendrites compared to in wild-type mice
• NMDAR-evoked excitatory postsynaptic current (eEPSC) decay time constants are almost twice as fast as in wild-type mice
• NMDAR-eEPSC amplitude is slightly reduced compared to in wild-type mice
• unlike in wild-type mice, Ro 25-6981 fails to inhibit eEPSC
• 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
• 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
• 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
• 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
• in a hidden platform Morris water maze but not when the platform is visible
• in a T maze, mice exhibit fewer spontaneous alternations compared with wild-type mice
• 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
• 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
• 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
• 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


Mouse Genome Informatics
cn8
    Lrp1tm2Her/Lrp1tm2Her
Tg(Camk2a-cre)T29-1Stl/0

involves: 129S7/SvEvBrd * BALB/c * C57BL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in the cortex of the brain at 12 months of age
• 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
• expression analysis indicates an age dependent decrease in synaptic density
• significant increase in apoptotic cells in the cortex and hippocampus at 24 months but not at 18 months of age
• 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
• 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
• severely reduced in hippocampal slices at 18 months of age

behavior/neurological
• exhibit significantly less freezing time than controls at 18 months of age
• exhibit significantly less freezing time than controls at 18 months of age
• develops by 13 months of age
• at 18 months of age
• in an open field test at 18 months of age

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

immune system
• 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
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:167724


Mouse Genome Informatics
cn9
    Arpc3tm1Ssod/Arpc3tm1Ssod
Tg(Camk2a-cre)T29-1Stl/0

involves: BALB/c * C57BL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit normal basal startle responses (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 in adolescent and adult mice in a novel object recognition test
• impaired in adolescent and adult mice in a novel object recognition test
• impaired in adult, but not adolescent, mice in a Y-maze
• in adult, but not adolescent, mice
• adult, but not adolescent, mice in the home cage
• in adult, but not adolescent, mice
• reduced social interaction of in adult, but not adolescent, mice

nervous system
• progressive loss of spine at P120
• neurons exhibit a decreased fraction of mushroom type spines and increased filopodia-like spines compared with control neurons
• 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
• in adolescent and adult mice


Mouse Genome Informatics
cn10
    Drd1tm2.1Stl/Drd1tm2.1Stl
Drd5tm1.1Stl/Drd5tm1.1Stl
Tg(Camk2a-cre)T29-1Stl/0

involves: BALB/c * C57BL * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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

nervous system
• 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


Mouse Genome Informatics
cn11
    Tg(ACTB-MAP2K1*K97M)1Stl/0
Tg(Camk2a-cre)T29-1Stl/0

involves: BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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%)
• 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
• 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
• 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
• 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
• ERK activation in the forebrain is inhibited, causing selective deficits in hippocampal memory retention and translation-dependent phase of late-LTP


Mouse Genome Informatics
cn12
    Crbntm1.1Jjh/Crbntm1.1Jjh
Tg(Camk2a-cre)T29-1Stl/0

involves: C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• mice exhibit normal basal locomotion and anxiety-like behaviors (J:179427)


Mouse Genome Informatics
cn13
    Grin1tm2Stl/Grin1tm2Stl
Tg(Actb-tTA)1Jzt/0
Tg(Camk2a-cre)T29-1Stl/0
Tg(tetO-Grin1/GFP)1Jzt/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 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
• 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)
• 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
• 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)


Mouse Genome Informatics
cn14
    Psen1tm1Jzt/Psen1tm1Jzt
Tg(Camk2a-cre)T29-1Stl/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• exposure to environmental enrichment following contextual fear conditioning results in a significant increase in freezing responses during retention tests

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

nervous system
• 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
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:73252


Mouse Genome Informatics
cn15
    Psen1tm1Jzt/Psen1tm1Jzt
Psen2tm1Ber/Psen2tm1Ber
Tg(Camk2a-cre)T29-1Stl/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• by 10 months of age mutants have impaired performance in a novel object recognition test
• by 10 months of age some mutants show increased activity in an open field test

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

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

nervous system
• the lateral ventricles are immensely enlarged compared to wild-type or single knockout mice
• the third ventricle is immensely enlarged compared to wild-type or single knockout mice
• the thickness of the corpus callosum is about a third that of controls
• the thickness of the molecular layers between the CA1 pyramidal cells and dentate gyrus is significantly reduced
• the cortex is about half the normal thickness and the 6 layers can no longer be distinguished
• increased Gfap expression indicates that reactive astrogliosis occurs along with forebrain degeneration
• changes in the expression of several markers indicate that neuronal atrophy occurs along with forebrain degeneration
• degeneration is seen in the forebrain

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 4 606889 J:90685
Alzheimer Disease; AD 104300 J:90685