Analysis Tools|
Allele Symbol Allele Name Allele ID |
Htttm6Mem targeted mutation 6, Marcy E MacDonald MGI:3697905 |
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| Summary |
4 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• exhibit movement abnormalities that are variable from week to week but do not worsen over time
• however, homozygotes do not develop paralysis or the progressive movement disorder seen in Hdhtm6Mem and Hdhtm8Mem compound heterozygotes
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• smaller throughout life
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some severely affected mutants die within 1 month of weaning
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• small throughout postnatal development and adulthood
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• mutants weigh significantly less at 1 week after birth and throughout adult life
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• develop a progressive movement disorder, with variable movement abnormalities evident from 2 months of age
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• first indications of movement abnormalities occur at around 2 months of age when mutants exhibit stiff tail and hindlimb clasping during tail suspension
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• over time, exhibit difficulties walking after handling
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• exhibit abnormal patterns of walking, including dragging hind limbs and a hopping gait that lacks normal alternating left-right steps
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• at the most advanced stages, most mutants become hypokinetic
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| N |
• mutants do not exhibit the striatal pathology that is seen in Huntington Disease
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• mutants show a range of ventricle sizes, however, ventricle size is not correlated with the progressive movement disease as mutants with normal sized ventricles develop the disease and some asymptomatic mutants have enlarged ventricles
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• between 2 and 19 months of age, about 50% of mutants have enlarged lateral and third ventricles, extending from the anterior striatum to the level of the hippocampus
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• between 2 and 19 months of age, about 50% of mutants have enlarged lateral and third ventricles, extending from the anterior striatum to the level of the hippocampus
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• exhibit increased sensitivity to anesthesia-induced death, tolerating only 50-80% of the dose delivered to controls
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| NOT | Huntington's disease | DOID:12858 |
OMIM:143100 |
J:72915 |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• exhibit movement abnormalities that are variable from week to week but do not worsen over time
• however, mutants do not develop paralysis or the progressive movement disorder seen in Hdhtm6Mem and Hdhtm8Mem compound heterozygotes
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• smaller throughout life
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• 3 of 7 adults have enlarged vesicles
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice administered tamoxifen after P21 exhibit progressive neurological abnormalities; all abnormalities reported below are in mice treated with tamoxifen from P21-P26
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• tamoxifen-treated mice exhibit clasping
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• mice administered tamoxifen from P21 to P26 exhibit abnormalities of motor coordination at 6 months of age
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• mice administered tamoxifen after P21 show Straub tail at one year of age
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• tamoxifen-treated mice exhibit gait disturbances at one year of age, including flattened pelvic elevation, abnormally wide hindlimb stance, and occasional hopping and stiffness
• gait abnormalities worsen over time such that 1-year-old mice lack the typical uniformity of step alternation and exhibit smaller gait strides
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• 1-year-old tamoxifen-treated mice exhibit smaller gait strides
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• mice administered tamoxifen from P21 to P26 exhibit a hyperkinetic phenotype at 6 months of age
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• tamoxifen-treated mice exhibit handling induced seizures, characterized by alternating clonic movement of forelimbs, clonic and versive movements of the head, chewing movement and facial myoclonus, flagpole tail dodrsiflexion, followed by intermittent eye blinking, immobility, head nodding and clonic mouth jerks
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• mice administered tamoxifen from P21 to P26 consistently show lower weight during adult life
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• 16-month-old mice exhibit atrophy of hindlimb muscles when tamoxifen is administered after P21
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• tamoxifen-treated mice exhibit handling induced seizures, characterized by alternating clonic movement of forelimbs, clonic and versive movements of the head, chewing movement and facial myoclonus, flagpole tail dodrsiflexion, followed by intermittent eye blinking, immobility, head nodding and clonic mouth jerks
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• the number of degenerating neurons in the outer cortical layers of tamoxifen-treated mice, especially in layer III/IV is increased
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• layer VI thickness and numbers of neurons are reduced in the motor cortex of 12-month-old tamoxifen-treated mice
• the number of degenerating neurons in the deep layer motor cortex are increased in 12-month-old tamoxifen-treated mice
• the reduction in motor cortex layer VI is seen as early as 3 months of age, however the number of neurons in layer VI is comparable to wild-type at this age
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• majority of tamoxifen-treated mice exhibit smaller cerebellar lobules
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• P21 mice show fewer APC+ smooth- and ramified-type oligodendrocytes
• 3-month-old mice show a reduction of smooth- and ramified-type oligodendrocytes in layer VI of the motor cortex, with an increase of stellar-type oligodendrocytes
• however, overall number of APC+ oligodendrocytes is normal in 3-month-old tamoxifen-treated mice
• oligodendrocyte progenitors derived from primary embryonic neuronal stem cells display progressive maturation abnormalities, with impairments in the transition from proliferating progenitors to post-mitotic precursors and subsequent maturation and myelination
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• 83.3% of 12-month-old tamoxifen-treated mice exhibit striatal reactive gliosis, with exceedingly severe gliosis in the globus pallidum
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• reactive astrogliosis in superficial and cortical layers already at 3 months of age
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• marker analysis indicates the presence of deficits in early neural lineage specification, migration, and regional organization, with impairments in the maturation of striatal compartmentalization
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• loss of the typical palisade appearance of pseudostratified neuroepithelium encompassing Mash1+ neuronal progenitors within the E15.5 lateral ganglionic eminence
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• all fetuses (E14.5, E15.5, and E17.5) and early postnatal mice (P2, P10, and P21) exhibit analogous masses consisting of heterotopic evaginations of germinative zone-derived cells from the posterior ventromedial aspect of the lateral ganglionic eminence indicating subpallial ventricular heterotopias
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• a number of non-degenerative cortical neurons of tamoxifen-treated mice, particularly those in layer III/IV, exhibit intracytoplasmic inclusions corresponding to concentric membrane-bound laminated inclusions of zebra bodies
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• tamoxifen-treated mice develop progressive striatal neurodegenerative pathology and cortical deep layer degeneration
• 27.3% of 12-month-old tamoxifen-treated mice show degenerative changes in the posterior ventrolateral striatum and the endopiriform claustrum
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• motor cortex of tamoxifen-treated mice shows axons of larger caliber displaying Wallerian-like degenerative morphology
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• 12-month-old tamoxifen-treated mice exhibit hypomyelinated axons in cortical deep layers, as well as axons with myelin balloons and tuberovesicular structures
• myelination defects preferentially affect axons of larger caliber, with reduced periodicity of myelin lamellae in large axons
• similar myelin defects are seen on white matter tracts containing axonal bundles traveling across the striatum
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• 16-month-old mice exhibit lordokyphosis when tamoxifen is administered after P21
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:260244 | |
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/12/2024 MGI 6.24 |
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