Phenotypes associated with this allele

• Allele Symbol: Tg(Eno2-cre)39Jme
• Allele Name: transgene insertion 39, Judith Melki
• Allele ID: MGI:2177175
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Rhot1^tm1.1Jmsu/Rhot1^tm1.1Jmsu Tg(Eno2-cre)39Jme/0	involves: 129 * C57BL/6 * C57BL/6J * SJL	MGI:5619354
cn2	Fxn^tm2Mkn/Fxn^tm2.1Mkn Tg(Eno2-cre)39Jme/0	involves: 129 * C57BL/6J	MGI:2177208
cn3	Smn1^tm1Jme/Smn1^tm1Jme Tg(Eno2-cre)39Jme/0	involves: 129 * C57BL/6J * SJL	MGI:5287852
cn4	Smn1^tm1Jme/Smn1^tm1.1Jme Tg(Eno2-cre)39Jme/0	involves: 129 * C57BL/6J * SJL	MGI:3721431
cn5	Pten^tm2Mak/Pten^tm2Mak Tg(Eno2-cre)39Jme/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:5660888
cn6	Slc12a6^tm2.1Dlp/Slc12a6^tm2.1Dlp Tg(Eno2-cre)39Jme/0	involves: 129S6/SvEvTac * C57BL/6J * SJL	MGI:5754620
cn7	Mtm1^tm1.2Jman/Y Tg(Eno2-cre)39Jme/?	involves: 129T1/Sv * C57BL/6 * SJL	MGI:3720806

Genotype
MGI:5619354

cn1

• Allelic Composition: Rhot1^tm1.1Jmsu/Rhot1^tm1.1Jmsu; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129 * C57BL/6 * C57BL/6J * SJL

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

mortality/aging

premature death ( J:216408 )

• premature death by around P35

growth/size/body

slow postnatal weight gain ( J:216408 )

• mice fail to gain weight with age

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:216408 )

• mice develop severe movement defects with age

limb grasping ( J:216408 )

• mice exhibit hindlimb clasping by P14

abnormal tail movements ( J:216408 )

• mice develop a stiff tail

spasticity ( J:216408 )

• mice develop hind-limb spasticity

nervous system

abnormal brainstem morphology ( J:216408 )

• brainstem and lumbar spinal regions contain aggregate bodies that are not seen in controls, resembling Bunina bodies which are eosinophilic inclusions

• Bunina-like structures appear to be extracellular

skeleton

kyphosis ( J:216408 )

• mice develop kyphosis with age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
motor neuron disease		DOID:231		J:216408

Genotype
MGI:2177208

cn2

• Allelic Composition: Fxn^tm2Mkn/Fxn^tm2.1Mkn; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129 * C57BL/6J

mortality/aging

premature death ( J:75420 )

• mutant mice die at 24 9 days after birth

behavior/neurological

abnormal motor coordination/balance ( J:75420 )

• mutant mice display loss of proprioception, as shown by the mis-positioning of the right hind-paw, which the mouse fails to perceive

ataxia ( J:75420 )

• mutant mice exhibit an average onset of ataxia at 12 days after birth

hunched posture ( J:75420 )

abnormal gait ( J:75420 )

• mutant mice develop a rapidly progressive gait abnormality

growth/size/body

cardiac hypertrophy ( J:75420 )

• at 2-3 weeks of age (shortly before or at death), mutants show a significantly increased mean heart to body weight ratio relative to wild-type mice (13.7 6 mg/g vs 5.8 0.5 mg/g, respectively)

decreased body weight ( J:75420 )

• mutant mice exhibit a low birth weight

weight loss ( J:75420 )

• mutants mice show progressive weight loss, with a 18% and 41% weight reduction noted at 7 days after birth and at death, respectively

• by P16, most mutants are moribund and rapidly stop gaining weight; some even rapidly lose weight

decreased body length ( J:75420 )

• at P12, mutants display reduced body length relative to wild-type mice; however, no obvious skeletal abnormalities are observed

postnatal growth retardation ( J:75420 )

• mutant mice display reduced growth rates throughout their lifespan relative to wild-type mice

muscle

muscle phenotype ( J:75420 )

N

abnormal myocardial fiber morphology ( J:75420 )

• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae

myocardium necrosis ( J:75420 )

dilated cardiomyopathy ( J:75420 )

cardiovascular system

abnormal myocardial fiber morphology ( J:75420 )

• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae

myocardium necrosis ( J:75420 )

cardiac hypertrophy ( J:75420 )

• at 2-3 weeks of age (shortly before or at death), mutants show a significantly increased mean heart to body weight ratio relative to wild-type mice (13.7 6 mg/g vs 5.8 0.5 mg/g, respectively)

cardiac fibrosis ( J:75420 )

dilated cardiomyopathy ( J:75420 )

cellular

dilated mitochondrion ( J:75420 )

• at 2 weeks, 50% of cardiac mitochondria appear to be swollen in the myofibrils

nervous system

neurodegeneration ( J:75420 )

• mutants exhibit areas of degeneration and necrosis in the dentate nucleus of the cerebellum and the brainstem (esp. in the trigeminal nucleus and tracts, the vestibular system and the cochlear nuclei and nerve)

• in contrast, the spinal cord, dorsal root ganglia and peripheral nerves appear unaffected

spongiform encephalopathy ( J:75420 )

abnormal nerve conduction ( J:75420 )

• upon electromyography, mutants show specific absence of the spinal somatosensory evoked response (H band), indicating a dysfunction in the large myelinated proprioceptive sensory neurons

• in contrast, the small myelinated sensory axons of the tail (heat and pain) have normal velocity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Friedreich ataxia		DOID:12705		J:75420

Genotype
MGI:5287852

cn3

• Allelic Composition: Smn1^tm1Jme/Smn1^tm1Jme; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129 * C57BL/6J * SJL

mortality/aging

premature death ( J:89836 )

• mutants die at an average of 31 days of age

nervous system

motor neuron degeneration ( J:89836 )

• progressive degeneration of motor nerves beginning at 20 days of age, with about 35% loss at 30 days in the phrenic nerve and about 45% in the facial nerve

• progressive degeneration is also seen in the trochlear nuclei and in the motoneurons of the spinal cord

• however, no loss of trigeminal or hypoglossal motoneurons is observed

abnormal facial nerve morphology ( J:89836 )

• progressive degeneration of the facial nerve such that at 30 days, 45% loss is observed

abnormal phrenic nerve morphology ( J:89836 )

• progressive degeneration of the phrenic nerves such that at 30 days, 35% loss is observed

axon degeneration ( J:89836 )

• progressive axon degeneration that begins at 20 days of age

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:89836 )

• mutants exhibit motor defects at two weeks of age

growth/size/body

weight loss ( J:89836 )

• mutants exhibit weight loss at two weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:89836

Genotype
MGI:3721431

cn4

• Allelic Composition: Smn1^tm1Jme/Smn1^tm1.1Jme; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129 * C57BL/6J * SJL

mortality/aging

premature death ( J:61396 )

• extremely reduced life expectancy, dying at a mean age of 25 days

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:61396 )

• severe motor defect evident at 2 weeks of age

impaired righting response ( J:61396 )

tremors ( J:61396 )

• evident at 2 weeks of age

abnormal limb posture ( J:61396 )

• abnormal posture of the hindlimbs

muscle

abnormal skeletal muscle fiber morphology ( J:61396 )

• presence of groups of atrophic muscle fibers and angular fibers intermixed with normal-size fibers

hypotonia ( J:61396 )

• severe hypotonia characterized by a defect of flexor muscles of the limbs and neck when suspended on a horizontal thread

nervous system

abnormal motor neuron morphology ( J:61396 )

• pronounced morphological changes of nuclei of motor neurons

• the presence of indentations of the nuclear membrane

• no significant loss of motor neurons of the anterior horns was detected in 2-weeks old mutant mice

abnormal motor neuron innervation pattern ( J:61396 )

• presence of a marked extrajunctional labeling of acetylcholine receptors indicating a denervation of skeletal muscle of neurogenic orgin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:61396

Genotype
MGI:5660888

cn5

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * SJL

behavior/neurological

abnormal behavior ( J:109635 )

• mutants are unusually resistant to handling by 6 weeks of age

impaired spatial learning ( J:109635 )

• in the Morris water maze, mutants learn the visible platform task as well as controls but show a trend toward slower acquisition

• in the submerged platform Morris water maze, mutants do not learn as quickly as controls, showing increased latency and longer distance traveled to reach the platform

• in the probe trial, mutants show no preference for time spent in each quadrant unlike controls which spend more time in the target quadrant

increased anxiety-related response ( J:109635 )

• mice show increased anxiety-like behavior in the open field where they spend less time in the center zone and show a lower ratio of center versus periphery time

• in the dark/light apparatus, mutants show longer latencies to enter the light side, spending most of their time on the dark side

• however, in the elevated plus maze, mutants do not show anxiety-like behavior

increased thigmotaxis ( J:109635 )

• mice exhibit a greater tendency to swim along the edge of the Morris water maze

increased startle reflex ( J:109635 )

• mutants exhibit increased initial startle responses to a 120 dB white noise stimulation

• however, mice show similar startle responses as controls upon repeated startle stimulation indicating normal habituation

increased locomotor activity ( J:109635 )

• mutants exhibit normal locomotor activity in less stressful environments but hyperactivity under more stressful conditions

• mice are hyperactive in the bright environment of the open field, traveling further at an increased average speed

• however, in the dark/light boxes and in the enclosed, darker environments of the locomotor apparatus, locomotor activity is normal

increased stereotypic behavior ( J:109635 )

• mice exhibit normal coordination on the accelerating rotarod test during initial trials, however they perform better during subsequent trials indicating better performance in a repetitive behavior

abnormal maternal nurturing ( J:109635 )

• mortality of pups by P5 from mutant females fertilized by wild-type males is increased, indicating defects in maternal care

abnormal nest building behavior ( J:109635 )

• mutants show little nest forming activity

abnormal sexual interaction ( J:109635 )

• no naive mutant males make female mice pregnant and active sexual behavior is not seen by males, however fertility of males is not analyzed

abnormal social investigation ( J:109635 )

• mice show decreased social interaction and abnormal social learing in several tests without change in novel object exploration, preference for social novelty, or olfaction

sporadic seizures ( J:109635 )

• 6 of 52 mutants exhibited sporadic seizures during testing

• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted

• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds

• sound and tactile stimuli do not induce seizures

growth/size/body

megacephaly ( J:109635 )

• mice show progressive macrocephaly, confined to the forebrain (cortex and hippocampus)

nervous system

sporadic seizures ( J:109635 )

• 6 of 52 mutants exhibited sporadic seizures during testing

• EEG/EMG recordings show that all mice develop spontaneous seizures during the light phase; repetitive spike-wave patterns, sometimes accompanied by rhythmic slow activity, and continuous spike-wave bursting are noted

• incidence of seizures is 0.67 per mouse per day, and the mean duration is 10 minutes 50 seconds

• sound and tactile stimuli do not induce seizures

increased brain weight ( J:109635 )

• progressive increase in brain weight after 2 months of age

abnormal hippocampus CA1 region morphology ( J:109635 )

• aging mice show compression or absence of the CA1 region

abnormal dentate gyrus morphology ( J:109635 )

• aging mice show foliation of the dentate gyrus

• disorganized dentate gyrus granular layer

• progressive increase in the thickness of MAP2+ dentate molecular layer

increased dentate gyrus size ( J:109635 )

• progressive enlargement with age

abnormal hippocampal mossy fiber morphology ( J:109635 )

• dentate gyrus shows progressive enlargement of the mossy fiber tract

• mice show elongated and dispersed mossy fiber tract from the granular layer of the dentate gyrus

thickened cerebral cortex ( J:109635 )

abnormal innervation ( J:109635 )

• ectopic neuronal processes extending from the cell bodies into the dentate gyrus polymorphic layer are seen in the dentate gyrus at 3 months of age

abnormal dendrite morphology ( J:109635 )

• dendritic hypertrophy and ectopy in adult dentate gyrus

• at 8 months of age, dendrites of ectopic neurons extending into the dentate gyrus polymorphic layer are longer and thicker and dendrites extending into the molecular layer are thicker

• at 8 months, dendritic arbors in the molecular layer of the dentate gyrus are increased in length

increased dendritic spine density ( J:109635 )

• 24.9% increase in dendritic spine density within the molecular layer of the dentate gyrus

abnormal synapse morphology ( J:109635 )

• synapses of the dentate gyrus are abnormal

• mossy fiber synapses span a larger area

abnormal synaptic vesicle number ( J:109635 )

• the dentate gyrus inner molecular layer shows an increase in presynaptic vesicle number

ectopic neuron ( J:109635 )

• at 8 months of age, ectopic neuronal processes extend into the polymorphic and molecular layers of the dentate gyrus

neuron hypertrophy ( J:109635 )

• Pten-negative neurons are larger than Pten-positive neurons at 4 weeks of age

• progressive increase in neuronal soma diameter indicating soma hypertrophy

reduced sensorimotor gating ( J:109635 )

• sensorimotor gating is impaired

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
macrocephaly-autism syndrome		DOID:0060867	OMIM:605309	J:109635

Genotype
MGI:5754620

cn6

• Allelic Composition: Slc12a6^tm2.1Dlp/Slc12a6^tm2.1Dlp; Tg(Eno2-cre)39Jme/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * SJL

behavior/neurological

behavior/neurological phenotype ( J:217087 )

N • surprisingly, mice display no locomotor deficit in the accelerated rotarod and open field tests relative to control mice

Genotype
MGI:3720806

cn7

• Allelic Composition: Mtm1^tm1.2Jman/Y; Tg(Eno2-cre)39Jme/?
• Genetic Background: involves: 129T1/Sv * C57BL/6 * SJL

normal phenotype

no abnormal phenotype detected ( J:81791 )

♂ • no obvious clinical symptom followed up to 14 weeks of age

♂ • no lesions were observed in muscle by histological analyses