Phenotypes associated with this allele
Allelic Composition |
Htttm1Mem/Htttm1Mem
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Genetic Background |
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htttm1Mem mutation
(1 available);
any
Htt mutation
(179 available)
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mortality/aging
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• by E8.5, all homozygous embryos are being resorbed, while only resorption sites are found at E9.5
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embryo
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• embryonic ectoderm is symmetrical and featureless, without evidence of head folds
• ectoderm is thicker than normal, and is disorganized rather than columnar especially distally
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• ~10% of cells are pyknotic compared to <1% in normal embryos
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• at E7.5, homozygous embryos are ~2/3 of normal size and misshapen; at E7.0, some homozygous embryos are observed to be smaller and thinner than other embryos in the litter
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• embryonic region appears shrunken at E7.5
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• at E7.5, primitive streak at one end of embryos forms, but no node structure is evident
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• at E7.5, there is prominent constriction between the extraembryonic and embryonic regions of homozygotes
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• at E7.5, extraembryonic region is reduced in size
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• columnar cells of endoderm are not organized into tight sheath as in normal embryos, but form a folded layer extending around shrunken embryonic region
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• mesoderm cells line yolk sac, amnion, and chorion, but do not extend to distal pole
• cells are abnormally rounded and densely, not loosely, packed
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growth/size/body
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• at E7.5, homozygous embryos are ~2/3 of normal size and misshapen; at E7.0, some homozygous embryos are observed to be smaller and thinner than other embryos in the litter
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cellular
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• ~10% of cells are pyknotic compared to <1% in normal embryos
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Allelic Composition |
Htttm1Mem/Htt+
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Genetic Background |
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CD-1 |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htttm1Mem mutation
(1 available);
any
Htt mutation
(179 available)
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normal phenotype
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• animals are normal is size and appearance, with no obvious behavioral or morphological abnormalities
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Allelic Composition |
Htttm1Mem/Htttm6Mem
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Genetic Background |
involves: 129S1/Sv * 129X1/SvJ * Swiss Webster |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htttm1Mem mutation
(1 available);
any
Htt mutation
(179 available)
Htttm6Mem mutation
(0 available);
any
Htt mutation
(179 available)
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behavior/neurological
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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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growth/size/body
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• smaller throughout life
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nervous system
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• 3 of 7 adults have enlarged vesicles
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Allelic Composition |
Htttm1Mem/Htttm7Mem
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Genetic Background |
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * CD-1 |
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htttm1Mem mutation
(1 available);
any
Htt mutation
(179 available)
Htttm7Mem mutation
(0 available);
any
Htt mutation
(179 available)
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mortality/aging
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• the expected numbers are seen at E18.5, however 7 of 18 are either dead or in the process of being absorbed, indicating that some die before E18.5
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• no mutants observed at weaning but some are present as stillborn pups
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nervous system
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• cerebellum is misshapen and appears underdeveloped
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• the tightly organized layer of neuroepithelium at the ventricular surface is absent or is replaced or obscured by Map2 immunoreactive postmitotic neuronal cells
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• midbrain is distorted by the abnormally large aqueduct
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• aqueduct is abnormally dilated
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• thalamus is malformed and displaced
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• along the midline, the entire septal area is misshapen and reduced
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• lateral ventricles are abnormally dilated
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• exhibit abnormal organization and thickening of the striatal subventricular zone
• however, the striatum does not show evidence of Huntington's disease-like pathology
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• hippocampus is malformed and displaced
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• agenesis of the fimbria
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• olfactory bulbs are malformed and displaced
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• display abnormal organization and thickening of the striatal subventricular zone that contains ectopic cell masses that protrude into the lateral ventricles
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• 4 of 11 fetuses exhibit exencephaly, with the forebrain and midbrain protruding from the open skull
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• fiber tracts exhibit extensive agenesis
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cardiovascular system
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• head region is conspicuously vascularized
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craniofacial
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• uni- or bilateral misplaced external ears
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• uni- or bilateral misshapen external ears
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hearing/vestibular/ear
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• uni- or bilateral misplaced external ears
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• uni- or bilateral misshapen external ears
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skeleton
integument
growth/size/body
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• pups alive at E18.5, display a more severe head phenotype than seen in Hdhtm7Mem homozygotes
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• uni- or bilateral misplaced external ears
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• uni- or bilateral misshapen external ears
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Allelic Composition |
Htttm1Mem/Htttm3Mem
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Genetic Background |
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * CD-1 |
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normal phenotype
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• appear normal; none display abnormal behaviors at 6 months of age
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Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Htttm1Mem mutation
(1 available);
any
Htt mutation
(179 available)
Htttm6Mem mutation
(0 available);
any
Htt mutation
(179 available)
Tg(CAG-cre/Esr1*)5Amc mutation
(9 available)
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behavior/neurological
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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growth/size/body
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• mice administered tamoxifen from P21 to P26 consistently show lower weight during adult life
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muscle
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• 16-month-old mice exhibit atrophy of hindlimb muscles when tamoxifen is administered after P21
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nervous system
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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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skeleton
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• 16-month-old mice exhibit lordokyphosis when tamoxifen is administered after P21
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