Mouse Genome Informatics
cn1
    Socs3tm1Ayos/Socs3tm1Ayos
Tg(Syn1-cre)671Jxm/0

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• on a high fat diet total fat weight and individual fat pad weights increase less in mutants compared to wild-type mice

behavior/neurological
• food intake is decreased on a high fat diet compared to wild-type mice on the same diet
• leptin treatment induces a greater decrease in food intake in mutants compared to wild-type mice

growth/size
• on a high fat diet mutants gain less weight
• treatment with leptin induces greater weight loss in mutants

homeostasis/metabolism
• after 22 weeks on a high fat diet plasma free fatty acid levels are significantly lower in mutants
• after 22 weeks on a high fat diet triglyceride levels are significantly lower in mutants
• glucose clearance is significantly faster in mutants compared to wild-type mice
• on a high fat diet mutants do not develop insulin resistance


Mouse Genome Informatics
cn2
    Leprtm1.1Chua/Leprtm1.1Chua
Tg(Syn1-cre)671Jxm/0

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism

endocrine/exocrine glands

nervous system
• sympathetic tone, as measured by Ucp1 expression and levels of epinephrine and norepinephrine, is low compared to in wild-type mice
• however, treatment with isoproterenol increases sympathetic tone


Mouse Genome Informatics
cn3
    Slc12a6tm1Garo/Slc12a6tm1Garo
Tg(Syn1-cre)671Jxm/0

involves: 129 * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• unable to successfully breed

nervous system
• progressive peripheral neuropathy starting at 3-4 weeks of age
• at 2 months of age
• hypoplastic with a small but significant decrease in length
• axon swelling in sciatic nerves
• axon degeneration, hypomyelination and axon swelling in sciatic nerves
• in sciatic nerves
• hypomyelination in sciatic nerves

behavior/neurological
• by 3-4 weeks of age
• severe locomotor deficiencies
• deficiencies become more severe after 8 months of age
• significant increase in the total distance traveled and the number of movement bouts at 5 months of age
• significantly less sensitive in a formalin test of spontaneous chemical/inflammatory pain

growth/size
• at 2 months of age

integument
• significantly less sensitive in a formalin test of spontaneous chemical/inflammatory pain


Mouse Genome Informatics
cn4
    Gabrb3tm2.1Geh/Gabrb3tm2.1Geh
Tg(Syn1-cre)671Jxm/?

involves: 129 * C57BL/6 * CBA * 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 61% died before weaning, many within a few days after birth

behavior/neurological
N
• homozygous mice that survived beyond weaning were normal and fertile (J:127877)
• unlike global knockout, they did not display foot clasping behavior, hyperactivity, seizures, or tremors (J:127877)
• less sensitive to the sedative/hypnotic effects of etomidate


Mouse Genome Informatics
cn5
    Bdnftm3Jae/Bdnftm3Jae
Tg(Syn1-cre)671Jxm/0

involves: 129/Sv * C57BL/6 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• an increased number of stimulations are required to initiate kindling behavior, however once initiated progression through subsequent classes of kindling is the same as in wild-type mice and no increase in the current required to induce the initial electrographic seizure is seen

nervous system
• an increased number of stimulations are required to initiate kindling behavior, however once initiated progression through subsequent classes of kindling is the same as in wild-type mice and no increase in the current required to induce the initial electrographic seizure is seen


Mouse Genome Informatics
cn6
    Ntrk2tm1Jom/Ntrk2tm1Jom
Tg(Syn1-cre)671Jxm/0

involves: 129/Sv * C57BL/6 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• kindling could not be induced even after 48 to 50 stimulations and an increase in the current required to induce the initial electrographic seizure is seen
• electroconvulsive shock can induce tonic-clonic seizures (the behavioral endpoint of kindling) in mutants

nervous system
• kindling could not be induced even after 48 to 50 stimulations and an increase in the current required to induce the initial electrographic seizure is seen
• electroconvulsive shock can induce tonic-clonic seizures (the behavioral endpoint of kindling) in mutants


Mouse Genome Informatics
cn7
    Ntrk2tm1Jom/Ntrk2+
Tg(Syn1-cre)671Jxm/0

involves: 129/Sv * C57BL/6 * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• a modest inhibition of kindling development is seen with an increased number of stimulations required to induce the third consecutive class 4 or class 5 seizure

nervous system
• a modest inhibition of kindling development is seen with an increased number of stimulations required to induce the third consecutive class 4 or class 5 seizure


Mouse Genome Informatics
cn8
    Leprtm1Rck/Leprtm1.1Rck
Tg(Syn1-cre)671Jxm/0

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue

growth/size
• increased adipose tissue mass and decreased lean tissue mass
• observed after 5 weeks of age

homeostasis/metabolism
• 2.3 fold greater plasma glucose levels in females compared to littermates; males normal
• hyperinsulinemia; 6 fold greater plasma insulin levels in males and 16.1 fold greater levels in females compared to littermates
• 5.8 fold greater in males and 8.3 fold greater in females compared to littermates

liver/biliary system
• enlarged liver due to fatty deposits


Mouse Genome Informatics
cn9
    Slc6a9tm1Veul/Slc6a9tm1Veul
Tg(Syn1-cre)671Jxm/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
muscle
N
• no hypotonia (J:161993)

behavior/neurological
N
• no motor defects seen in open field or rotarod tests (J:161993)

nervous system
• GlyT1 specific uptake of glycine by hippocampal membranes is reduced 50%


Mouse Genome Informatics
cn10
    Atrtm1Bal/Atrtm2Bal
Tg(Syn1-cre)671Jxm/0

involves: 129S/SvEv * 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• tamoxifen-treated mice do not show any significant differences from controls in circadian activity, strength, motor coordination, anxiety-like behavior, learning or memory (J:123200)


Mouse Genome Informatics
cn11
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac
Tg(Syn1-cre)671Jxm/?

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 6 and 8 weeks

homeostasis/metabolism
• diabetic in one week
• extremely elevated


Mouse Genome Informatics
cn12
    Nf1tm1Par/Nf1tm1Par
Tg(Syn1-cre)671Jxm/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• body weight and size are about 50% of normal
• 3-4 days after birth, mice begin to exhibit growth retardation that is sustained into adulthood

nervous system
• forebrain, but not the rest of the brain, is reduced in size, however mice exhibit normal neuronal development
• increase in cell density in the cerebral cortex, often resulting in less apparent lamination
• about 20% reduction in coritcal thickness
• mice display astrogliosis in various brain regions, however do not develop neuronal degeneration or microgliosis

behavior/neurological
• mice display severe learning disability

tumorigenesis
N
• no evidence of tumors; optic gliomas, astrocytomas, or neurofibroma are not observed (J:68558)

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:68558


Mouse Genome Informatics
cn13
    Kif5atm1Gsn/Kif5atm2Gsn
Tg(Syn1-cre)671Jxm/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 72% of mutant mice die of seizures at ~3 weeks of age, between P15 and P25
• the remaining ~28% (8 of 29) of mutant mice survived to >3 months of age; one died at 3 months, one at 4 months, and another at 5.5 months, while the rest were sacrified at 5.5, 7, and 8 months

growth/size
• by 2-3 weeks of age, mutant mice are obviously smaller than control littermates
• at 3 weeks of age, mutant body weight is only ~50% of control weight

behavior/neurological
• at 3 weeks of age, mutant mice frequently display a tremor, although their posture is relatively normal
• all mutant mice surviving to >5 months of age, develop tremors while walking
• at 3 weeks of age, mutant mice fall off the rotarod more frequently than control mice
• all mutant mice surviving to >5 months of age develop abnormal hindlimb posture at rest
• however, a relatively normal posture is observed until ~5 months of age
• mutant mice surviving to >5 months of age develop a partial hindlimb paralysis
• 72% of mutant mice die from spontaneous seizures lasting 20-30 seconds
• repetitive seizures and stress-induced seizures are also observed

nervous system
• 72% of mutant mice die from spontaneous seizures lasting 20-30 seconds
• repetitive seizures and stress-induced seizures are also observed
• mutant mice surviving to >5 months of age display a striking degeneration of sensory axons within L5 lumbar dorsal roots along with numerous profiles of myelin debris
• at 3 weeks of age, mutants show a ~14% loss of sensory axon numbers within L5 dorsal roots, with a preferrential (60%) loss of large caliber sensory axons (>3 Ám in diameter) but no significant loss of small caliber axons
• by 5.5 months of age, mutants exhibit a ~12% loss of motor axons and a profound 36% loss of sensory axons; again, sensory and motor axon loss is most severe for large caliber axons (>4 Ám), and loss of ventral root axons is not as profound as that observed in the dorsal root
• at 5.5 months of age, the peak of the distribution of the diameter of large caliber axons in the ventral root shifts from 7-7.5 Ám in controls to 5.5-6 Ám in mutants
• in the dorsal roots, severe axon loss is noted in sensory axons with calibers >2 Ám, with complete loss of the largest sensory axons (>7 Ám), but no loss of small caliber sensory axons (<1.5 Ám)
• at 3 weeks of age, mutant mice show a a specific deficit in the slow axonal transport of neurofilaments, as evidenced by the accumulation of NF subunits (NF-H, NF-L, and NF-M) and peripherin in the cell bodies of DRG sensory neurons
• however, no obvious changes in the amounts of NF-H, NF-M, NF-L, or peripherin are detected in the brain and sciatic nerve of mutant mice
• in addition, fast axonal transport appears to be intact, as markers of several fast axonal transport pathways (APP, Rab3, and synaptophysin) appeared unchanged in the DRG and in sciatic nerve ligation experiments

homeostasis/metabolism
• at 3 weeks of age, mutant mice display a striking accumulation of neurofilament (NF) subunits (NF-H, NF-L, and NF-M) and peripherin in the cell bodies of dorsal root ganglion (DRG) sensory neurons, due to a specific deficit in slow axonal transport of NFs
• neurofilament accumulation in the DRG is accompanied by a significant decrease in the number of large caliber sensory axons
• betaIII-tubulin is unchanged in younger animals, but displays behavior indicative of defective transport in some older mutant mice
• notably, accumulation of NF subunit levels in the DRG is not accompanied by obvious reductions in the sciatic nerve


Mouse Genome Informatics
cn14
    Ogttm1Gwh/Y
Tg(Syn1-cre)671Jxm/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• none survive for more than 10 days (J:93112)
• found at only about 50% of the expected frequency (J:93112)

behavior/neurological
• rarely nurse (J:93112)
• fail to develop normal locomotor activity (J:93112)

growth/size


Mouse Genome Informatics
cn15
    Ogttm1Gwh/Ogttm1Gwh
Tg(Syn1-cre)671Jxm/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• none survive for more than 10 days (J:93112)

behavior/neurological
• rarely nurse (J:93112)
• fail to develop normal locomotor activity (J:93112)

growth/size


Mouse Genome Informatics
cn16
    Fig4tm1.1Mm/Fig4tm1.1Mm
Tg(Syn1-cre)671Jxm/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival to 5 months of age but severely weakened

behavior/neurological
• severe movement disorder by 30 days of age
• both forelimb and hind limb clasping in tail suspension tests at 3 months of age

nervous system
• low level of astrocyte dysfunction
• in deep layers of cortex, cerebellar nuclei, hippocampus, brainstem, and dorsal root ganglia

growth/size
• body weight reductions are modest, weights of about 17g

integument
N
• normal coat color (not diluted) (J:185989)


Mouse Genome Informatics
cn17
    Ntf3tm1Esm/Ntf3tm1Esm
Tg(Syn1-cre)671Jxm/0

involves: 129S1/Sv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• mutants exhibit normal synaptic transmission, with no differences in paired-pulse facilitation, post-tetanic potentiation, or long-term potentiation (J:82354)


Mouse Genome Informatics
cn18
    Tsc1tm1Djk/Tsc1tm1.1Djk
Tg(Syn1-cre)671Jxm/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival of 35 days, with no survivors beyond 65 days (J:121858)
• mice treated with rapamycin or RAD001 (mTOR inhibitor) show 90-100% survival to 80 days of age compared to median survival of 33 days for untreated mutants (J:136366)
• discontinuation of drug treatment at P30 results in clinical symptom improvement for 1-2 weeks followed by clinical deterioration and death at 79 days for rapamycin-treated and 77 days for RAD001-treated mutants (J:136366)

growth/size
• after P5 until death, mutants fail to gain weight at same rate as controls; average maximum weight is 10 grams

nervous system
• mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe
• severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds
• after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death
• only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso
• enlarged cells are seen outside cerebral cortex, in other parts of brain including thalamus, hypothalamus and brainstem
• no increased cell loss or degeneration is observed in regions containing anomalous enlarged cells
• brain weight to body weight ratio is significantly greater (2.4-fold) in mutants compared to wild-type; with rapamycin/RAD001 treatment, difference from control is significantly reduced but still observed
• enlarged cells are observed in hilus
• enlarged cells are seen throughout pyramidal cell layer, particularly in CA3 region
• enlarged ectopic cells are seen outside the CA1-CA3 fields in stratum oriens and stratum radiatum
• laminar organization is less distinct than in the 6 cortical layers of controls (J:121858)
• unusually large cells are observed in all six layers in mutants, particularly in layer V; layer of enlarged cells is seen at gray-white matter border throughout cerebral cortex at P21 (J:121858)
• mutants display subset of enlarged pS6-positive cells at base of cortex and in cortical layer V; drug treatment results in marked reduction in size of enlarged cells (J:136366)
• mild cortical disorganization is observed in mutants with or without rapamycin treatment (J:136366)
• contains some enlarged cells
• Nissl bodies and filamentous aggregates are often detected in enlarged neurons, prominently in brainstem but rarely in enlarged cortical cells (J:121858)
• some neurons are aberrantly localized outside primary pyramidal cell layers; ectopic neurons are isolated, not organized into clusters or columns (J:121858)
• some neurons in somatosensory cortex show 60% increase in soma size relative to controls (J:121858)
• many pyramidal neurons demonstrate dysplastic features including increased size and thicker dendritic arbors compared to control neurons (J:121858)
• population of neurons in lateral somatosensory cortex are considerably enlarged compared with those in controls; size is significantly reduced after drug treatment (from 1.8-fold to 1.2-fold), but effect reverses when treatment is stopped (J:136366)
• in somatosensory cortex, layer V neurons often have major dendrites extending tangentially and diagonally to the pia, in contrast to control neurons which mainly have long apical dendrite oriented directly toward pial surface; rapamycin treatment initiated at P7 does not significantly decrease abnormally oriented dendrite percentage (J:136366)
• in mutant brains, neurons appear to be still actively growing after P14-21, whereas wild-type neurons have stopped growing
• this may result in the hypomyelination, due to secondary myelination failure
• in hippocampal neuron cultures, neuronal dendritic spine density is reduced >20% compared to controls
• with rapamycin treatment, spine density is marginally increased; spine length however is increased 9% compared to treated and untreated controls or untreated mutants
• hypomyelination is observed in brains of mutants (J:121858)
• oligodendrocyte number and distribution appears similar to wild-type (J:121858)
• myelination particularly in cortex is impaired due to decreased myelin production by oligodendrocytes; rapamycin treatment works to restore myelination throughout brain with greatest improvement in cortex and hippocampus (J:136366)
• mice aged P21-48 display 3 types of electrographic abnormalities: short spike bursts observed in all mice examined, occasionally spontaneous period of desynchronization with electrodecrement and at low incidence, frequent high-amplitude sharp waves
• interictal (seizure) 1-2 second bursts of high-amplitude 7-8 hertz spikes are observed with high frequency compared with controls; these are without obvious clinical correlate

behavior/neurological
• clasping behavior and tremor are significantly ameliorated by rapamycin/RAD001 treatment relative to untreated animals at 30, 60, and 100 days postnatal
• apparent by P10
• display posterior limb-clasping behavior when lifted by tail
• progressive high-frequency trunk and limb tremor apparent by P10
• at death, usually in third to fifth postnatal week, mice are found with extensor posture of fore- and hindlimbs
• develops by by third or fourth postnatal week
• apparent by P10
• mice show progressive decline in activity with limited mobility by third or fourth postnatal week
• tail dorsiflexion is exhibited
• mice develop clinical seizures, spontaneous and some provoked in most part by physical simulation; both types of seizures are mild or severe
• severe seizures are characterized by brief behavioral arrest, followed by several seconds of clonic activity, followed by tonic extensor posturing of trunk and limbs for 15-45 seconds
• after P21, suspension by the tail results in gentle spinning leading severe seizure activity, followed by bradycardia and death
• only mild seizures occur spontaneously, characterized by brief myoclonic jerking of head and torso

skeleton
• kyphosis is significantly improved in rapamycin/RAD001-treated mice compared with untreated mutants

cellular
• in mutant brains, neurons appear to be still actively growing after P14-21, whereas wild-type neurons have stopped growing
• this may result in the hypomyelination, due to secondary myelination failure

Mouse Models of Human Disease
OMIM IDRef(s)
Tuberous Sclerosis 1; TSC1 191100 J:136366


Mouse Genome Informatics
cn19
    Tsc1tm1Djk/Tsc1tm1Djk
Tg(Syn1-cre)671Jxm/0

involves: 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• clinical features, survival, and brain pathology are stated to be identical to that of Tsc1tm1DjkTsc1tm1.1DjkTg(Syn1-cre)671Jxm conditional mutants; however no data are presented

growth/size

nervous system

behavior/neurological


Mouse Genome Informatics
cn20
    Kif5atm1.2Noh/Kif5atm1.2Noh
Tg(Syn1-cre)671Jxm/0

involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die at approximately 3 weeks postnatally

nervous system
N
• mice exhibit normal brain histology (J:197666)
• mice exhibit epileptic electroencephalography (EEG) and reduced EEG power during rest and locomotive states compared with control mice
• impaired neurotransmission in the hippocampus with abnormal post-Golgi GABA receptor trafficking and localization
• reduced mean amplitude with a shift to smaller amplitudes
• however, miniature inhibitory postsynaptic currents frequency, rise time and decay time are normal

growth/size

behavior/neurological
• mice exhibit epileptic electroencephalography (EEG) and reduced EEG power during rest and locomotive states compared with control mice


Mouse Genome Informatics
cn21
    Lrp1tm2Her/Lrp1tm2Her
Tg(Syn1-cre)671Jxm/0

involves: 129S7/SvEvBrd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die around 9 months of age

reproductive system
• greatly reduced fertility

behavior/neurological
• adults eat more compared to wild-type controls
• a constant muscle tremor develops by 3 weeks of age
• pronounced hind limb weakness, unable to stand on their hind legs
• develop dystonic posturing over time
• over time increased plantar flexion of the feet occurs, with asymmetric involvement in some mice
• general hyperactivity combined with increased voluntary movement, detectable by 3 weeks of age
• waddling gait
• step width increases in relation to step length

skeleton
• increased thoracic kyphosis develops over time

growth/size
• adults are leaner than wild-type controls
• initially similar in size and weight to wild-type controls but gradually fall behind in their growth rate

adipose tissue
• adults are leaner than wild-type controls

homeostasis/metabolism

nervous system
N
• no histological defects in brain morphology are detected (J:93329)
• electroencephalographic and electromyographic studies confirmed the tremor but did not detect any abnormalities in neuro- or neuromuscular transmission (J:93329)
• no abnormalities in hippocampal long term potentiation are detected (J:93329)


Mouse Genome Informatics
cn22
    Nkx2-1tm2Shk/Nkx2-1tm2Shk
Tg(Syn1-cre)671Jxm/0

involves: 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• female mutants exhibit a shorter reproductive span than control females, with 50% of mutant dams ceasing to deliver pups by 6-9 months of age

reproductive system
• female mutants exhibit a shorter reproductive span than control females, with 50% of mutant dams ceasing to deliver pups by 6-9 months of age
• female mutants display delayed puberty, defined as the age at which the first ovulation takes place, relative to control females
• however, the onset of vaginal opening is normal relative to control littemates
• reproductive defects are associated with reduced hypothalamic expression of genes critical for sexual development and deregulation of a gene involved in restraining puberty
• female mutants deliver their first litter ~2 weeks later than control females, consistent with a 10-day delay in first ovulation assessed by the age at first estrus (J:116686)
• however, mating behavior appears unaffected (J:116686)
• female mutants show a significantly delayed initiation of cyclicity relative to control females (J:116686)
• however, no differences in body weight gain are observed over a 240-day period relative to control females (J:116686)
• the length of the first estrous cycle is nearly three times longer than in wild-type controls (J:116686)
• subsequent estrous cycles are slightly longer in duration (5-6 days) relative to cycles in control littermates (4-5 days) (J:116686)
• 50% of female mutants fail to become pregnant by 6-9 months of age, whereas >90% of control females reproduce normally at this age (J:116686)
• mutant dams produce fewer pups than control dams in a 1-year period (J:116686)
• the total number of litters produced by each mutant dam every 90 days is reduced by ~50% by 3 months of age (J:116686)
• however, pups born to mutant females appear normal and show normal birth weights relative to controls (J:116686)

behavior/neurological
N
• adult mutant exhibit normal novel object recognition as well as normal learning and memory, as assessed by the water maze and passive avoidance tests, indicating that basal forebrain cholinergic neuronal function is essentially intact (J:116686)
• unexpectedly, adult mutants display higher, instead of lower, measures of anxiety than wild-type mice in the elevated zero maze test
• adult mutants exhibit reduced novel location recognition relative to wild-type mice
• however, novel object recognition remains intact relative to wild-type mice
• at 14 months of age, adult mutants are able to stay longer on the rotarod than wild-type mice
• unexpectedly, adult mutants exhibit higher, rather than lower, locomotor activity than age-matched wild-type controls in the open field test

nervous system
N
• mutants display normal basal ganglia/hypothalamic morphology relative to control littermates (J:116686)
• no extrapyramidal deficits associated with basal ganglia dysfunction are observed (J:116686)


Mouse Genome Informatics
cn23
    Sema3ftm1.1Ddg/Sema3ftm1.1Ddg
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the anterior limb of the anterior commissure is defasciculated
• 1 of 5 mutants exhibit improper development of the infrapyramidal tract
• most axons of the anterior limb of the anterior commissure cross the midline aberrantly and axons of the infrapyramidal tract extend beyond the stratum oriens of CA3
• however, no defects in stria terminalis targeting
• 1 of 5 mutants exhibit an infrapyramidal tract defect in which axons extend far into the stratum oriens of CA3, beyond the level at which they normally turn dorsally into the stratum radiatum
• the anterior limb of the anterior commissure is reduced and defasciculated
• although a small number of axons of the anterior commissure decussate properly, most axons cross the midline aberrantly as smaller tightly bundled fascicles

cellular
• the anterior limb of the anterior commissure is defasciculated


Mouse Genome Informatics
cn24
    Sema3ftm1.1Ddg/Sema3ftm1.2Ddg
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• the anterior limb of the anterior commissure is defasciculated
• 2 of 3 mutants exhibit improper development of the infrapyramidal tract
• most axons of the anterior limb of the anterior commissure cross the midline aberrantly and axons of the infrapyramidal tract extend beyond the stratum oriens of CA3
• however, no defects in stria terminalis targeting
• 2 of 3 mutants exhibit an infrapyramidal tract defect in which axons extend far into the stratum oriens of CA3, beyond the level at which they normally turn dorsally into the stratum radiatum
• the anterior limb of the anterior commissure is reduced and defasciculated
• although a small number of axons of the anterior commissure decussate properly, most axons cross the midline aberrantly as smaller tightly bundled fascicles

cellular
• the anterior limb of the anterior commissure is defasciculated


Mouse Genome Informatics
cn25
    Plrg1tm2Jcbr/Plrg1tm2Jcbr
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival at P3 is 25% compared to 88% for wild-type mice
• all mice die by P9

nervous system

cellular


Mouse Genome Informatics
cn26
    Prkar2btm3Gsm/Prkar2btm2Gsm
Tg(Syn1-cre)671Jxm/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
N
• locomotor behavior restored to normal (J:196157)

growth/size
N
• body weight restored to normal (J:196157)

adipose tissue
N
• major fat pads are comparable to controls (J:196157)


Mouse Genome Informatics
cn27
    Gt(ROSA)26Sortm1(CAG-EGFP/Vamp2)Gcg/Gt(ROSA)26Sor+
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice are phenotypically indistinguishable from control littermates


Mouse Genome Informatics
cn28
    Tg(Syn1-cre)671Jxm/0
Ubqln1tm1.1Hmw/Ubqln1tm1.1Hmw

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• slower recovery of motor function after ischemic injury
• increased ischemia/reperfusion-caused brain injury in 2 months old animals
• increased accumulation of ubiquitinated-proteins

homeostasis/metabolism
• slower recovery of motor function after ischemic injury
• increased ischemia/reperfusion-caused brain injury in 2 months old animals


Mouse Genome Informatics
cn29
    Hgstm2Tkh/Hgstm2Tkh
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6 * CBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system

nervous system
• the number of neurons undergoing apoptosis in the CA3 region is increased compared to in wild-type mice
• at 5 weeks of age, mice exhibit a loss of pyramidal neurons in the CA3 region that progressively worsens with age unlike in wild-type mice
• however, the numbers of pyramidal cells in the CA1 region and mossy fiber attachments are normal
• pyramidal neuron loss is due to increased apoptosis of cells

behavior/neurological
• mice exhibit increased time immobilized during a swim test despite normal muscle strength
• mice exhibit a reduced latency to entering in a dark box compared to wild-type mice in a passive avoidance test

growth/size
• begining at 3 weeks
• by 8 weeks of age, mice cease to gain weight unlike wild-type mice

cellular
• the number of neurons undergoing apoptosis in the CA3 region is increased compared to in wild-type mice


Mouse Genome Informatics
cn30
    Tg(ACTB-NOTCH1)1Shn/0
Tg(Syn1-cre)671Jxm/0

involves: C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
N
• no increase in apoptosis is seen at E13.5 in the telencephalon of double transgenic mice (J:90392)


Mouse Genome Informatics
cn31
    S1pr1tm1Jch/S1pr1tm1Jch
Tg(Syn1-cre)671Jxm/?

involves: C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• response to Experimental Autoimmune Encephalitis induced by Myelin Oligodendrocyte Glycoprotein is similar to controls (J:168824)