Analysis Tools|
Allele Symbol Allele Name Allele ID |
Tg(HDexon1)62Gpb transgene insertion 62, Gillian Bates MGI:2386951 |
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| Summary |
11 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• as in Tg(HDexon1)62Gpb mice
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• as in Tg(HDexon1)62Gpb mice
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• as in Tg(HDexon1)62Gpb mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit premature death compared with wild-type mice but improved survival compared with Tg(HDexon1)62Gpb mice
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• impaired performance on a rotarod is delayed until 13 weeks of age compared with 10 weeks as in Tg(HDexon1)62Gpb mice
• improved beam walking compared with Tg(HDexon1)62Gpb mice
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• as in Tg(HDexon1)62Gpb mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants had more huntingtin protein aggregates within the cerebral cortex and striatum but no difference in the onset of motor dysfunction and the mean lifespan compared to Tg(HDexon1)62Gpb transgenic mice
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• mutants had more huntingtin protein aggregates within the cerebral cortex and striatum but no difference in the onset of motor dysfunction and the mean lifespan compared to Tg(HDexon1)62Gpb transgenic mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mean lifespan of mutants was increased by 19.7% compared Tg(HDexon1)62Gpb transgenic mice
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• mutants showed a delayed onset of motor dysfunction compared to Tg(HDexon1)62Gpb transgenic mice at 9, 10, and 11 weeks of age
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• 10 week-old mutants had 30-35% more huntingtin protein aggregates within the cerebral cortex and striatum than Tg(HDexon1)62Gpb transgenic mice
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• 10 week-old mutants had 30-35% more huntingtin protein aggregates within the cerebral cortex and striatum than Tg(HDexon1)62Gpb transgenic mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
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• significantly reduced at 12 weeks of age
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• mice exhibit left ventricular dilation in comparison to controls
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• detected as early as 8 weeks of age and reduced to 50% by 12 weeks of age
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• mice exhibit progressive reduction in stroke volume, although there are no differences in heart rate
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• transmitral flow velocity is altered as compared to controls
• E/A ratio is significantly decreased at all time points
• mice exhibit a decrease in passive ventricular filling and a significant increase in atrial-mediated left ventricle filling
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• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
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• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
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• mice exhibited less weight gain over time than controls
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• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
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• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
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• exhibit clasping of both fore and hind paws
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• impaired mobility in home cages
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• 3-hydroxykynurenine (3-HK) levels are significantly elevated in the striatum at 4 weeks of age, a phenotype observed in Huntington disease patients
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• 3-HK levels are significantly elevated in the cortex at 4 weeks of age, a phenotype observed in Huntington disease patients
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• 3-HK levels are significantly elevated in the cerebellum at 4 weeks of age, a phenotype observed in Huntington disease patients
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• striatal and cortical mitochondria are equally resistant to calcium at 8 and 12 weeks of age, while in controls, striatal mitochondria is more sensitive to calcium
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• striatal and cortical neurons display more rapid and increased swelling to N-methyl-D-aspartate (NMDA) than controls, but not to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or kainate (KA), indicating increased sensitivity to NMDA
• intracellular recordings show that resting membrane potentials of striatal neurons are significantly more depolarized than in controls
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:99425 , J:111237 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased preference for dark in dark/light choice test at 12 and 14 weeks of age
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• beginning at 4 weeks of age
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• mice exhibit a reduced latency to fall on rotarod test beginning at 4 weeks of age as compared to wild-type
• latency time decreases with age
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• progressive deterioration of grip strength especially in males between 10-14 weeks of age
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• wider base (separation between legs) than controls; females exhibit difference earlier than males
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• decreased stride length (ipsilateral) observed at 8 weeks of age
• shorter splay length (contralateral) than controls
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• mice rear less in the center of the open field test than controls at all ages in the light phase and by 6 weeks of age in the dark phase
• mice exhibit a progressive decrease in climbing activity starting at 4 weeks of age
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• mice are hypoactive in the open field test in both the light and dark phases of the light cycle
• in the light phase females are less active at 8 and 14 weeks of age
• in the light phase males are less active starting at 6 weeks of age
• in the dark phase both sexes are hypoactive beginning at 12 weeks of age
• progressive hypoactivity is observed in the center of the open field beginning at 4 weeks of age
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• decrease in body weight is observed by 7 weeks in both genders
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• median survival of 113 days
• all mice die within 12 weeks of the first death
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• observed after 8 weeks of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• increased preference for dark in dark/light choice test at 14 weeks of age
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• observed at 6 and 14 weeks of age in both genders
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• mice exhibit a progressive impairment on the rotarod test beginning at 8 weeks of age
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• progressive deterioration of grip strength especially in males at 14 weeks of age
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• narrower base (separation between legs) than controls
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• shorter splay length (contralateral) than controls at 14 weeks of age
• stride length (ipsilateral) is similar to controls
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• mice rear less in the center of the open field test than controls starting at 12 weeks of age in the light phase
• rearing is similar to controls in dark phase
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• mice cover less total distance in light phase of open field test starting at 6 weeks of age in females and 8 weeks of age in males
• in dark phase, hypoactivity is significant at 6 weeks of age in both genders
• mice cover less distance in center starting at 12 weeks in light phase and 6 weeks in dark phase
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• body weight decreases by 10 weeks of age in females and 9 weeks in males
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• median survival of 141 days for females and 179 days for males
• all mice die within 9 weeks of the first death
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• observed at 14 weeks of age, especially in females
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• reduction in brain weight by 5 weeks
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• immunoreactive htt is detected in the striatum at 4.5 weeks
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• immunoreactive htt is detected in the cortex beginning at 3.5 weeks
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• striatal neurons have prominent and frequent indentations of the nuclear membrane and an apparent increase in the clustering and number of nuclear pores by 10-12 weeks of age
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• inclusions are observed within neurons of cerebral cortex, striatum, cerebellum, spinal cord and to a much lesser degree in the hippocampus, thalamus, globus pallidus and substantia nigra
• inclusions appear in the cerebral cortex before they can be detected in the striatum
• inclusions are ubiquitinated by 5-6 weeks and can be detected by ultrastructural analysis by 8 weeks
• htt immunoreactive inclusions are seen in approximately 20% of neurons
• in the striatum, ultrastructural analysis of inclusions reveals a prominent, roughly circular, pale structure
• inclusions are granular with occasional filamentous structures around the periphery; they are larger than the nucleolus and occupy 1% of nuclear volume
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• progressive loss of body weight
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:42085 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• retinal dysplasia covers more than 50% of the entire retina
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• misplaced photoreceptor nuclei are seen in the segment layers at 10 weeks of age
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• inner segment is reduced in thickness at 10 weeks of age
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• seen at 10 weeks of age
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• outer segment is reduced in thickness at 10 weeks of age
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• seen at 10 weeks of age
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• outer nuclear layer of the retina exhibits an irregular and wavy shape, disrupted with folds and whorls at 10 weeks of age
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• misplaced photoreceptor nuclei are seen in the outer plexiform layer at 10 weeks of age
• however, no inner plexiform layer or ganglion cell layer abnormalities
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• misplaced photoreceptor nuclei are seen in the segment layers at 10 weeks of age
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• inner segment is reduced in thickness at 10 weeks of age
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• seen at 10 weeks of age
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• outer segment is reduced in thickness at 10 weeks of age
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• seen at 10 weeks of age
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• nuclear inclusions are seen in the retina
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• usually between 10 to 13 weeks of age
• mice can die suddenly
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• average of 19% smaller than wildtype
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• dyskinesia of limbs when suspended by the tail
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• progressive resting tremor in limbs, trunk and head
• involuntary jerky shudders
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• mice lose balance when sitting on hind limbs, turning and grooming their backs
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• onset of motor impairment as early as 4 weeks of age
• stereotypic repetitive stroking of the nose and face, hind limb kicking and scratching movement
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• 2 distinct characteristic vocalizations observed
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• islets exhibit huntingtin inclusions in 24% of cells by 12 weeks of age
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• islets exhibit huntingtin inclusions in 19% of cells by 7 weeks of age, by week 12 frequency is greater than 95%
• islets are hypotrophic by 12 weeks, BrdU incorporation is reduced 6-fold
• significant reduction in insulin and somatostatin content by 12 weeks
• islets are smaller in size by 12 weeks
• islets contain few insulin secretory vesicles by 12 weeks
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• by 12 weeks, no signs of apoptosis or necrosis are observed
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• islets exhibit huntingtin inclusions in 6% of cells by 12 weeks of age
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• small seminal ducts and gland size
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• body weight declines after 10 weeks
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• body weight is normal at weaning
• with progression of phenotype up to 30% of body weight can be lost
• overall loss of muscle bulk observed
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• abnormal glucose homeostasis
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• insulin secretion in response to glucose and KCl is decreased 4-fold and 2.5-fold, respectively, by 12 weeks of age
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• identified at 11.5 weeks of age, insulin response absent
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• small seminal ducts and gland size
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• smaller size ovaries and uteri often observed
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:36689 | |
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 12/10/2024 MGI 6.24 |
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