Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rhot1tm1.1Jmsu mutation
(0 available);
any
Rhot1 mutation
(43 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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mortality/aging
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• premature death by around P35
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growth/size/body
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• mice fail to gain weight with age
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behavior/neurological
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• mice develop severe movement defects with age
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• mice exhibit hindlimb clasping by P14
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• mice develop a stiff tail
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• mice develop hind-limb spasticity
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nervous system
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• 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
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skeleton
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• mice develop kyphosis with age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Fxntm2.1Mkn mutation
(0 available);
any
Fxn mutation
(40 available)
Fxntm2Mkn mutation
(0 available);
any
Fxn mutation
(40 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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mortality/aging
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• mutant mice die at 24 9 days after birth
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behavior/neurological
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• mutant mice display loss of proprioception, as shown by the mis-positioning of the right hind-paw, which the mouse fails to perceive
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• mutant mice exhibit an average onset of ataxia at 12 days after birth
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• mutant mice develop a rapidly progressive gait abnormality
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growth/size/body
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• 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)
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• mutant mice exhibit a low birth weight
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• 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
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• at P12, mutants display reduced body length relative to wild-type mice; however, no obvious skeletal abnormalities are observed
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• mutant mice display reduced growth rates throughout their lifespan relative to wild-type mice
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muscle
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• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae
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cardiovascular system
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• at 2 weeks, mutant cardiac muscle contains numerous lipid droplets and giant mitochondria with disorganized cristae
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• 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)
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cellular
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• at 2 weeks, 50% of cardiac mitochondria appear to be swollen in the myofibrils
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nervous system
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• 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
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Smn1tm1Jme mutation
(3 available);
any
Smn1 mutation
(86 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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mortality/aging
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• mutants die at an average of 31 days of age
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nervous system
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• 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
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• progressive degeneration of the facial nerve such that at 30 days, 45% loss is observed
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• progressive degeneration of the phrenic nerves such that at 30 days, 35% loss is observed
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• progressive axon degeneration that begins at 20 days of age
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behavior/neurological
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• mutants exhibit motor defects at two weeks of age
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growth/size/body
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• mutants exhibit weight loss at two weeks of age
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mortality/aging
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• extremely reduced life expectancy, dying at a mean age of 25 days
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behavior/neurological
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• severe motor defect evident at 2 weeks of age
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• evident at 2 weeks of age
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• abnormal posture of the hindlimbs
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muscle
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• presence of groups of atrophic muscle fibers and angular fibers intermixed with normal-size fibers
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• severe hypotonia characterized by a defect of flexor muscles of the limbs and neck when suspended on a horizontal thread
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nervous system
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• 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
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• presence of a marked extrajunctional labeling of acetylcholine receptors indicating a denervation of skeletal muscle of neurogenic orgin
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm2Mak mutation
(4 available);
any
Pten mutation
(81 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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behavior/neurological
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• mutants are unusually resistant to handling by 6 weeks of age
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• 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
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• 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
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• mice exhibit a greater tendency to swim along the edge of the Morris water maze
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• 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
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• 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
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• 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
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• mortality of pups by P5 from mutant females fertilized by wild-type males is increased, indicating defects in maternal care
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• mutants show little nest forming activity
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• no naive mutant males make female mice pregnant and active sexual behavior is not seen by males, however fertility of males is not analyzed
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• mice show decreased social interaction and abnormal social learing in several tests without change in novel object exploration, preference for social novelty, or olfaction
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• 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
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growth/size/body
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• mice show progressive macrocephaly, confined to the forebrain (cortex and hippocampus)
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nervous system
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• 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
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• progressive increase in brain weight after 2 months of age
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• aging mice show compression or absence of the CA1 region
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• aging mice show foliation of the dentate gyrus
• disorganized dentate gyrus granular layer
• progressive increase in the thickness of MAP2+ dentate molecular layer
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• progressive enlargement with age
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• 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
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• 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
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• 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
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• 24.9% increase in dendritic spine density within the molecular layer of the dentate gyrus
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• synapses of the dentate gyrus are abnormal
• mossy fiber synapses span a larger area
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• the dentate gyrus inner molecular layer shows an increase in presynaptic vesicle number
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• at 8 months of age, ectopic neuronal processes extend into the polymorphic and molecular layers of the dentate gyrus
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• Pten-negative neurons are larger than Pten-positive neurons at 4 weeks of age
• progressive increase in neuronal soma diameter indicating soma hypertrophy
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• sensorimotor gating is impaired
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Slc12a6tm2.1Dlp mutation
(0 available);
any
Slc12a6 mutation
(120 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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behavior/neurological
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• surprisingly, mice display no locomotor deficit in the accelerated rotarod and open field tests relative to control mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mtm1tm1.2Jman mutation
(0 available);
any
Mtm1 mutation
(27 available)
Tg(Eno2-cre)39Jme mutation
(2 available)
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normal phenotype
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• no obvious clinical symptom followed up to 14 weeks of age
• no lesions were observed in muscle by histological analyses
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Analysis Tools