|
Allele Symbol Allele Name Allele ID |
Tg(HDexon1)62Gpb transgene insertion 62, Gillian Bates MGI:2386951 |
||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
11 genotypes
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• as in Tg(HDexon1)62Gpb mice
|
|
• as in Tg(HDexon1)62Gpb mice
|
|
• as in Tg(HDexon1)62Gpb mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mice exhibit premature death compared with wild-type mice but improved survival compared with Tg(HDexon1)62Gpb mice
|
|
• 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
|
|
• as in Tg(HDexon1)62Gpb mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• 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
|
|
• 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
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mean lifespan of mutants was increased by 19.7% compared Tg(HDexon1)62Gpb transgenic mice
|
|
• mutants showed a delayed onset of motor dysfunction compared to Tg(HDexon1)62Gpb transgenic mice at 9, 10, and 11 weeks of age
|
|
• 10 week-old mutants had 30-35% more huntingtin protein aggregates within the cerebral cortex and striatum than Tg(HDexon1)62Gpb transgenic mice
|
|
• 10 week-old mutants had 30-35% more huntingtin protein aggregates within the cerebral cortex and striatum than Tg(HDexon1)62Gpb transgenic mice
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
|
|
• significantly reduced at 12 weeks of age
|
|
• mice exhibit left ventricular dilation in comparison to controls
|
|
• detected as early as 8 weeks of age and reduced to 50% by 12 weeks of age
|
|
• mice exhibit progressive reduction in stroke volume, although there are no differences in heart rate
|
|
• 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
|
|
• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
|
|
• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
|
|
• mice exhibited less weight gain over time than controls
|
|
• mitochondria in cardiomyocytes examined at 12 weeks of age exhibit a circular appearance with a disruption of uniform densities
|
|
• diminished left ventricular wall motion during systole
• left ventricle fractional shortening significantly impaired at 10 and 12 weeks of age
|
|
• exhibit clasping of both fore and hind paws
|
|
• impaired mobility in home cages
|
|
• 3-hydroxykynurenine (3-HK) levels are significantly elevated in the striatum at 4 weeks of age, a phenotype observed in Huntington disease patients
|
|
• 3-HK levels are significantly elevated in the cortex at 4 weeks of age, a phenotype observed in Huntington disease patients
|
|
• 3-HK levels are significantly elevated in the cerebellum at 4 weeks of age, a phenotype observed in Huntington disease patients
|
|
• 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
|
|
• 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
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:99425 , J:111237 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased preference for dark in dark/light choice test at 12 and 14 weeks of age
|
|
• beginning at 4 weeks of age
|
|
• 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
|
|
• progressive deterioration of grip strength especially in males between 10-14 weeks of age
|
|
• wider base (separation between legs) than controls; females exhibit difference earlier than males
|
|
• decreased stride length (ipsilateral) observed at 8 weeks of age
• shorter splay length (contralateral) than controls
|
|
• 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
|
|
• 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
|
|
• decrease in body weight is observed by 7 weeks in both genders
|
|
• median survival of 113 days
• all mice die within 12 weeks of the first death
|
|
• observed after 8 weeks of age
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• increased preference for dark in dark/light choice test at 14 weeks of age
|
|
• observed at 6 and 14 weeks of age in both genders
|
|
• mice exhibit a progressive impairment on the rotarod test beginning at 8 weeks of age
|
|
• progressive deterioration of grip strength especially in males at 14 weeks of age
|
|
• narrower base (separation between legs) than controls
|
|
• shorter splay length (contralateral) than controls at 14 weeks of age
• stride length (ipsilateral) is similar to controls
|
|
• 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
|
|
• 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
|
|
• body weight decreases by 10 weeks of age in females and 9 weeks in males
|
|
• median survival of 141 days for females and 179 days for males
• all mice die within 9 weeks of the first death
|
|
• observed at 14 weeks of age, especially in females
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• reduction in brain weight by 5 weeks
|
|
• immunoreactive htt is detected in the striatum at 4.5 weeks
|
|
• immunoreactive htt is detected in the cortex beginning at 3.5 weeks
|
|
• 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
|
|
• 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
|
|
• progressive loss of body weight
|
Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Huntington's disease | DOID:12858 |
OMIM:143100 |
J:42085 | |
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• retinal dysplasia covers more than 50% of the entire retina
|
|
• misplaced photoreceptor nuclei are seen in the segment layers at 10 weeks of age
|
|
• inner segment is reduced in thickness at 10 weeks of age
|
|
• seen at 10 weeks of age
|
|
• outer segment is reduced in thickness at 10 weeks of age
|
|
• seen at 10 weeks of age
|
|
• outer nuclear layer of the retina exhibits an irregular and wavy shape, disrupted with folds and whorls at 10 weeks of age
|
|
• 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
|
|
• misplaced photoreceptor nuclei are seen in the segment layers at 10 weeks of age
|
|
• inner segment is reduced in thickness at 10 weeks of age
|
|
• seen at 10 weeks of age
|
|
• outer segment is reduced in thickness at 10 weeks of age
|
|
• seen at 10 weeks of age
|
|
• nuclear inclusions are seen in the retina
|
|
|
| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
|
• usually between 10 to 13 weeks of age
• mice can die suddenly
|
|
• average of 19% smaller than wildtype
|
|
• dyskinesia of limbs when suspended by the tail
|
|
• progressive resting tremor in limbs, trunk and head
• involuntary jerky shudders
|
|
• mice lose balance when sitting on hind limbs, turning and grooming their backs
|
|
• 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
|
|
• 2 distinct characteristic vocalizations observed
|
|
• islets exhibit huntingtin inclusions in 24% of cells by 12 weeks of age
|
|
• 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
|
|
• by 12 weeks, no signs of apoptosis or necrosis are observed
|
|
• islets exhibit huntingtin inclusions in 6% of cells by 12 weeks of age
|
 |
• small seminal ducts and gland size
|
 |
|
|
|
|
|
• body weight declines after 10 weeks
|
|
• 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
|
|
• abnormal glucose homeostasis
|
|
• insulin secretion in response to glucose and KCl is decreased 4-fold and 2.5-fold, respectively, by 12 weeks of age
|
|
• identified at 11.5 weeks of age, insulin response absent
|
|
|
• small seminal ducts and gland size
|
|
|
|
|
|
• smaller size ovaries and uteri often observed
|
|
|
|
|
|
|
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) |
||
|
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support. |
last database update 04/30/2024 MGI 6.23 |
|
|
|
||
Analysis Tools