Mouse Genome Informatics
tg
    Tg(HDexon1)61Gpb/?
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
nervous system
• striatal neurons have prominent and frequent indentations of the nuclear membrane and an apparent increase in the clustering and number of nuclear pores
• males with a CAG repeat length of 134-138 exhibit a 2-fold increase in c-Fos positive neurons in the forebrain and hindbrain (J:203027)
• 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
• 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

behavior/neurological
• impaired performance in location recognition test is observed by 14 weeks of age
• in the last of a series of Barnes circular maze trials, the time required to locate the escape tunnel is increased in 12 week old transgenic mice as compred to wildtype
• 12 week old transgenic mice raised in an enriched environment perform as well as non-enriched wildtype in circular maze trials
• in the last of a series of Barnes circular maze trials, the time required to locate the escape tunnel is increased in 12 week old transgenic mice as compared to wildtype
• 12 week old transgenic mice raised in an enriched environment perform as well as non-enriched wildtype in circular maze trials
• transgenic mice use both serial and spatial search strategies in the ultimate trials of the circular maze as compared to wildtype and enriched transgenic mice, which primarily use spatial search strategies
• beginning at 12 weeks of age, transgenic mice exhibit a deficit in short term memory as evaluated by performance in the Y-maze
• males with 134-138 CAG repeats exhibit progressive development of motor abnormalities (J:203027)
• in males with 134-138 CAG repeats (J:203027)
• between 8-12 weeks of age, transgenic mice perform on the rotarod as well as wildtype, however, by 14 weeks performance decreases and by 20 weeks performance is significantly impaired

cardiovascular system
• males with 134-138 CAG repeats exhibit a smaller left ventricular cardiomyocyte diameter at 3 and 7 months of age (J:203027)
• however, no signs of cardiomyocyte disarray or overt fibrosis (J:203027)
• males with 134-138 CAG repeats show an absence of 24 hour variation of heart rate that is seen in wild-type mice and higher heart rate levels in both the dark and light phases at 3.5 months of age, but lower heart rate during the active (dark) phase at 6.5 months of age (J:203027)
• 3.5 month old males with 134-138 CAG repeats exhibit a slower restoration of heart rate towards baseline in response to shake stress test (J:203027)
• 6.5 month old males with 134-138 CAG repeats show a tendency for a reduced peak change in heart rate response to the shake stress test and slower recovery towards the baseline (J:203027)
• heart rate response to the beta-adrenergic agonist isoproterenol is attenuated in 6.5 month old conscious males with 134-138 CAG repeats (J:203027)
• the blunted heart rate response to isoproterenol in mutants is normalized to wild-type levels by atropine pre-treatment (J:203027)
• males with 134-138 CAG repeats show sinus arrhythmia at 3.5 and 6.5 months of age (J:203027)
• in males with 134-138 CAG repeats at 3.5 and 6.5 months of age (J:203027)
• males with 134-138 CAG repeats exhibit unstable heart rate compared to wild-type mice, showing chaotic heart rate rhythm and irregular beat-to-beat R-R intervals (J:203027)
• males with 134-138 CAG repeats show a variety of arrhythmias at 3.5 and 6.5 months of age, including atrial-ventricular conduction blockade, sinus arrhythmia, atrial flutter, atrial fibrillation, supra-ventricular and ventricular premature beats, and short episodes of ventricular tachycardia (J:203027)
• in males with 134-138 CAG repeats at 3.5 and 6.5 months of age (J:203027)
• in males with 134-138 CAG repeats at 3.5 and 6.5 months of ag (J:203027)
• males with 134-138 CAG repeats show a variety of arrhythmias at 3.5 and 6.5 months of age, including atrial-ventricular conduction blockade (J:203027)
• males with 134-138 CAG repeats exhibit unstable RR intervals that are reversed following atropine treatment (J:203027)
• males with 134-138 CAG repeats exhibit cessation of body weight gain prior to the age when they exhibit typical motor abnormalities (J:203027)

growth/size/body
• males with 134-138 CAG repeats exhibit cessation of body weight gain prior to the age when they exhibit typical motor abnormalities (J:203027)

homeostasis/metabolism
• males with 134-138 CAG repeats show 6-fold higher plasma levels of noradrenaline at 7, but not 3.5, months of age (J:203027)
• noradrenaline content in the left ventricle of males with 134-138 CAG repeats is 40% lower at 7 months of age (J:203027)

mortality/aging
• 3 of 16 males die at 6-7 months of age due to sudden cardiac death (J:203027)

muscle
• males with 134-138 CAG repeats exhibit a smaller left ventricular cardiomyocyte diameter at 3 and 7 months of age (J:203027)
• however, no signs of cardiomyocyte disarray or overt fibrosis (J:203027)

Mouse Models of Human Disease
OMIM IDRef(s)
Huntington Disease; HD 143100 J:42085 , J:203027