Phenotypes associated with this allele

• Allele Symbol: Htt^tm5Detl
• Allele Name: targeted mutation 5, Peter J Detloff
• Allele ID: MGI:6400708
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htt^tm5Detl/Htt^tm5Detl	involves: C57BL/6	MGI:6400709
ht2	Htt^tm5Detl/Htt^+	involves: C57BL/6	MGI:6400710

Genotype
MGI:6400709

hm1

• Allelic Composition: Htt^tm5Detl/Htt^tm5Detl
• Genetic Background: involves: C57BL/6

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

mortality/aging

prenatal lethality, complete penetrance ( J:250587 )

• mice die in utero as no homozygous pups are seen

Genotype
MGI:6400710

ht2

• Allelic Composition: Htt^tm5Detl/Htt⁺
• Genetic Background: involves: C57BL/6

behavior/neurological

behavior/neurological phenotype ( J:250587 )

N • mice do not exhibit signs of tremor, hunching, unsteady movements or staggering gait up to 70 weeks of age and do not exhibit spontaneous or handling-induced seizures

abnormal motor learning ( J:250587 )

♂ • males, but not females, exhibit enhanced fast motor learning (performance on the rotarod across all 3 testing days) at 40 and 60 weeks of age

increased thigmotaxis ( J:250587 )

♀ • females, but not males, spend increased time along the walls of the test chamber, indicating increased thigmotaxis and possible anxiety

impaired coordination ( J:250587 )

♂ • at 60 weeks of age, males, but not females, show a reduction in motor coordination on the 2nd and 3rd days of testing on the accelerating rotarod, with a shorter latency to fal

decreased grip strength ( J:250587 )

• males and females exhibit reduced grip strength, with a significant decrease in females at 50 weeks of age

hunched posture ( J:250587 )

♀ • females spend more time with their bodies contracted, or hunched, at nearly all ages

abnormal gait ( J:250587 )

• females, but not males, show a reduction in hind paw step cycle

• males, but not females, show a reduction in front paw base of support at 60 weeks of age, indicating reduced stability

long stride length ( J:250587 )

♂ • males, but not females, show an increase in front paw stride length

decreased locomotor activity ( J:250587 )

• mice exhibit an overall decrease in spontaneous locomotion during the active dark phase, with females being more severely affected than males at 70 weeks of age

• however, no differences in spontaneous activity during the light phase are seen

growth/size/body

weight loss ( J:250587 )

• mice show reduced weight by 70 weeks of age

• males exhibit a 9.4% reduced body weight by 40 weeks of age while females exhibit a 9.4% reduced body weight by 30 weeks of age

mortality/aging

prenatal lethality, incomplete penetrance ( J:250587 )

• fewer than the expected number of pups are seen, indicating reduced viability

nervous system

abnormal striatum morphology ( J:250587 )

• females, but not males, show a reduction in striatal DARPP-32 (a neuropathological maker of Huntingtons Disease pathogenesis) expression with no cell loss

• however, no differences in synaptophysin or CB1 receptor expression in the striatum are seen

• Htt aggregates are seen in the striatum, at similar levels in males and females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:250587