Phenotypes Associated with This Genotype

Genotype
MGI:7266814

• Allelic Composition: Htt^tm1Mem/Htt^tm6Mem; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * Swiss Webster

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

behavior/neurological

behavior/neurological phenotype ( J:260244 )

N • mice administered tamoxifen after P21 exhibit progressive neurological abnormalities; all abnormalities reported below are in mice treated with tamoxifen from P21-P26

limb grasping ( J:260244 )

• tamoxifen-treated mice exhibit clasping

impaired coordination ( J:260244 )

• mice administered tamoxifen from P21 to P26 exhibit abnormalities of motor coordination at 6 months of age

straub tail ( J:260244 )

• mice administered tamoxifen after P21 show Straub tail at one year of age

abnormal gait ( J:260244 )

• 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

short stride length ( J:260244 )

• 1-year-old tamoxifen-treated mice exhibit smaller gait strides

hyperactivity ( J:260244 )

• mice administered tamoxifen from P21 to P26 exhibit a hyperkinetic phenotype at 6 months of age

environmentally induced seizures ( J:260244 )

• 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

growth/size/body

decreased body weight ( J:260244 )

• mice administered tamoxifen from P21 to P26 consistently show lower weight during adult life

muscle

muscular atrophy ( J:260244 )

• 16-month-old mice exhibit atrophy of hindlimb muscles when tamoxifen is administered after P21

nervous system

environmentally induced seizures ( J:260244 )

• 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

abnormal cerebral cortex morphology ( J:260244 )

• the number of degenerating neurons in the outer cortical layers of tamoxifen-treated mice, especially in layer III/IV is increased

abnormal primary motor cortex morphology ( J:260244 )

• 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

abnormal cerebellum lobule morphology ( J:260244 )

• majority of tamoxifen-treated mice exhibit smaller cerebellar lobules

abnormal oligodendrocyte morphology ( J:260244 )

• 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

gliosis ( J:260244 )

• 83.3% of 12-month-old tamoxifen-treated mice exhibit striatal reactive gliosis, with exceedingly severe gliosis in the globus pallidum

astrocytosis ( J:260244 )

• reactive astrogliosis in superficial and cortical layers already at 3 months of age

abnormal nervous system development ( J:260244 )

• marker analysis indicates the presence of deficits in early neural lineage specification, migration, and regional organization, with impairments in the maturation of striatal compartmentalization

abnormal lateral ganglionic eminence morphology ( J:260244 )

• loss of the typical palisade appearance of pseudostratified neuroepithelium encompassing Mash1+ neuronal progenitors within the E15.5 lateral ganglionic eminence

ectopic neuron ( J:260244 )

• 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

neuronal cytoplasmic inclusions ( J:260244 )

• 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

neurodegeneration ( J:260244 )

• 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

axon degeneration ( J:260244 )

• motor cortex of tamoxifen-treated mice shows axons of larger caliber displaying Wallerian-like degenerative morphology

dysmyelination ( J:260244 )

• 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

skeleton

lordokyphosis ( J:260244 )

• 16-month-old mice exhibit lordokyphosis when tamoxifen is administered after P21

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:260244