Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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mortality/aging
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• Background Sensitivity: median survival is 1.5 days, similiar to survival on the 129S1/Sv background but longer than on a mixed 129S1/Sv and C57BL/6J background and shorter than on mixed 129S1/Sv/CD-1/ICR and mixed 129S1/Sv/DBA/2J backgrounds
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cellular
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• E18.5 mutants exhibit nuclear envelope bleb formation in the cortex (8%), striatum (6%), and cerebellum (71%)
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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mortality/aging
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• homozygotes typically die within 48 hours after birth
(J:107596)
• Background Sensitivity: median survival is 1.5 days, longer than on a mixed 129S1/Sv and C57BL/6 background but shorter than on a mixed 129S1/Sv/CD-1/ICR or mixed 129S1/Sv and DBA/2J background
(J:185289)
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cellular
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• lumen of the nuclear envelope contains large numbers of vesicles that appear to derive from the inner nuclear membrane; ventral horn neurons are most affected
(J:107596)
• E18.5 mutants exhibit nuclear envelope bleb formation in the cortex (7%), striatum (1.2%), and cerebellum (81%)
(J:185289)
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behavior/neurological
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• homozygous pups fail to feed after birth
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• homozygous pups do not vocalize after birth
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nervous system
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• hippocampal neurons exhibit an accelerated cytoplasmic calcium concentration decay compared to controls
• treatment with glutamate-receptor antagonist does not affect the accelerated decay seen in neurons
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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mortality/aging
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• Background Sensitivity: median lifespan is 0.5 days, shorter than on a 129S1/Sv background or other backgrounds studied
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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mortality/aging
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• Background Sensitivity: median lifespan is 2.5 days and all mutants die by P3.5; survival is longer than on the 129S1/Sv or mixed 129S1/Sv and C57BL/6 background
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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mortality/aging
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• Background Sensitivity: median survival is 3.5 days, although survival up to 21 days is seen and 13.2% live longer than 7 days; survival is longer than any of the other backgrounds studied, including on the 129S1/Sv or a mixed 129S1/Sv and C57BL/6J background
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behavior/neurological
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• pups do not feed well and appear generally ill
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• mutants that live through the end of the first postnatal week develop abnormal motor behavior, showing tremor and prolonged twisting movements gait, particularly of the hindlimbs
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• mutants that live through the end of the first postnatal week develop abnormal motor behavior, showing tremor and prolonged twisting movements gait, particularly of the hindlimbs
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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Abnormal white matter microstructure in Tor1atm2Wtd/Tor1a+ mice
nervous system
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• abnormal white matter microstructure, showing a reduction in fractional anisotropy, a magnetic resonance diffusion tensor imaging index of axonal integrity and coherence
• white matter abnormalities are localized to the right superior cerebellar tract, the white matter subjacent to the right primary sensorimotor cortex, and the left caudate/putamen
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• fractional anisotropy reduction in the caudate/putamen
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• Purkinje cells show subtle abnormalities among the dendritic trees, showing fewer dendrites and shorter total dendritic lengths
• dendritic spines in Purkinje cells appear thinner and less complex, showing a 14% lower spine density in mutants and 5% lower spine density in females compared to males
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• mutants exhibit 33% more heterotopic Purkinje cells in the cerebellum than controls
• heterotopic Purkinje cells are more frequent in the caudal cerebellum compared to the anterior cerebellum
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• FDG microPET indicates a single brain region with abnormal glucose utilization localized to the superior cerebellar vermis, with increased local metabolic activity
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• subtle enlargement of the cerebellum, with total volume of the cerebellum including granule cell layer, molecular cell layer, and deep cerebellar nuclei is slightly increased
• however, no structural abnormality of deep cerebellar nuclei neurons or Purkinje cell numbers
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• reduction of tract numbers in cerebellothalamic (-49%), thalamocortical (-55%) and thalamostriatal (-86%) projection pathways
• fewer tracts, with fiber count reductions, in the rostral (-59%) and caudal (-86%) pontocerebellar pathways
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behavior/neurological
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N |
• males exhibit normal motor activity in the open field and habituate similar to wild-type males, normal rotarod behavior and similar performance to wild-type on the beam-walking test
• males do not display altered responses to drug challenge
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Allelic
Composition |
Tor1atm2Wtd/Tor1a+
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Genetic
Background |
involves: 129S1/Sv |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
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cellular
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• nuclear envelope is normal compared to homozygous Tor1a homozygous or compound mutants
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nervous system
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• hippocampal neurons exhibit a prolonged cytoplasmic calcium concentration decay, indicating that neurons experience calcium overload
• treatment with glutamate-receptor antagonist results in the ablation of this prolonged decay
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behavior/neurological
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N |
• males have no apparent behavioral abnormalities
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cellular
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• lumen of the nuclear envelope contains large numbers of vesicles that appear to derive from the inner nuclear membrane
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tor1atm2Wtd mutation
(1 available);
any
Tor1a mutation
(22 available)
Tor1atm4.2Wtd mutation
(0 available);
any
Tor1a mutation
(22 available)
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behavior/neurological
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• truncal twisting during tail suspension
• sustained forepaw straining during tail suspension
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• forelimb clasping during tail suspension
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• balance beam crossing using forepaws and dragging hind paws
• increased number of footslips on balance beam as compared to control
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• balance beam crossing using forepaws and dragging hind paws
• increased number of footslips on balance beam as compared to control
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• impaired ability to remain suspended in horizontal grid hang test (decreased latency to fall)
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• hunched posture on balance beam
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growth/size/body
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• reduced body weight beginning at P7 as compared to controls
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mortality/aging
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• 47.37% survival rate
• most of loss occurs by 30 days of age
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nervous system
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• reduced numbers of deep cerebellar nuclei
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• regions of gliosis found in deep cerebellar nuclei, cortex, thalamus, red nucleus and facial motor nucleus
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• ubiquitin accumulation found in deep cerebellar nuclei, cortex, thalamus, red nucleus and facial motor nucleus
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vision/eye
nervous system
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N |
• cortical thickness is normal and mice have normal numbers of CUX1+ (cortical layer II-IV) and CTIP2+ (cortical layer V-VI) cells
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nervous system
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• cortical thickness is normal at birth but is dramatically reduced by P28, with mice showing a nonsignificant reduction of CUX1+ (cortical layer II-IV) cortical neurons and a significant reduction of CTIP2+ (cortical layer V-VI) cortical neurons at P28
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behavior/neurological
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• mice show increased limb clasping in the tail suspension test
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nervous system
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• cortical thickness is reduced
• however, CUX1+ (cortical layer II-IV) and CTIP2+ (cortical layer V-VI) cortical neuron counts are normal
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behavior/neurological
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N |
• mice show almost complete rescue of the abnormal postural (squinty eyes and twisted hindpaws) and development phenotypes seen in Tor1atm2Wtd/Tor1atm3.1Wtd Tg(Nes-cre)1Kln/0 mice
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growth/size/body
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N |
• mice exhibit partial rescue of the postnatal growth retardation seen in Tor1atm2Wtd/Tor1atm3.1Wtd Tg(Nes-cre)1Kln/0 mice from P8 to P28 and are fully restored to normal weight by P56
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nervous system
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N |
• mice do not exhibit neurodegeneration or gliosis
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behavior/neurological
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• forelimb clasping
• action-induced forepaw clenching during tail suspension
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• mice develop spontaneous abnormal movements by second postnatal week
• unilateral twisted hind paw
• bilateral twisted hind paws
• prolonged stiff extension of hind limbs
• abnormal toe postures
• tail extension
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• mice exhibit an increase in the number of footslip/cross in beam crossing
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• 4 of 7 mice show twisted hindpaws at P15
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growth/size/body
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• mice are significantly smaller than littermate controls
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• reduced postnatal growth
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muscle
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• mice develop spontaneous abnormal movements by second postnatal week
• unilateral twisted hind paw
• bilateral twisted hind paws
• prolonged stiff extension of hind limbs
• abnormal toe postures
• tail extension
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nervous system
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• loss of red nucleus by P56
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• minimal gliosis is observed in spinal cord
(J:213785)
• reactive gliosis is observed at P56 in deep layers of the sensorimotor cortex, ventral posterior thalamus, globus pallidus, deep cerebellar nuclei, red nucleus and facial nerve nuclei and is less severe than gliosis found in null mice
(J:213785)
• reactive gliosis in the cortex and thalamus
(J:288753)
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• abnormal accumulation of perinuclear ubiquitin
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• striatal cholinergic interneuron degeneration
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vision/eye
behavior/neurological
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• hindlimb and forelimb clasping observed by P15, however, with maturity clasping decreases
• forepaw clenching during tail suspension observed by P15
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• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous twisting of hind paws
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• mice exhibit an increase in number of footslip/cross in beam crossing
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muscle
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• twisted truncal postures observed by P15, however, mice do not exhibit spontaneous twisting of hind paws
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nervous system
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• decrease in neuron number in red nucleus and deep cerebellar nuclei (DCN) as compared to controls
• neuron loss in DCN is 2 fold less in this genotype as compared to mice carrying Tor1atm1Wtd allele
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• neurodegeneration is milder in in this genotype as compared to mice carrying Tor1atm1Wtd allele
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Analysis Tools