Phenotypes associated with this allele

• Allele Symbol: Htt^tm1Hay
• Allele Name: targeted mutation 1, Michael Hayden
• Allele ID: MGI:2177743
• Summary: 9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htt^tm1Hay/Htt^tm1Hay	involves: C57BL/6J	MGI:3586835
ht2	Htt^tm1Hay/Htt^+	involves: C57BL/6J	MGI:3586839
cx3	Htt^tm1Hay/Htt^tm1Hay Tg(HTT*97Q)IXwy/0 Tg(YAC18)18Hay/Tg(YAC18)18Hay	FVB.Cg-Htt^tm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay	MGI:5617271
cx4	Htt^tm1Hay/Htt^tm1Hay Tg(YAC128)53Hay/0	involves: C57BL/6J * FVB	MGI:3711011
cx5	Htt^tm1Hay/Htt^tm1Hay Tg(YAC353G6)W7Hay/0	involves: C57BL/6J * FVB/NJ	MGI:3711010
cx6	Htt^tm1Hay/Htt^tm1Hay Tg(YAC72)2511Hay/0	involves: FVB/N	MGI:5298845
cx7	Htt^tm1Hay/Htt^+ Tg(YAC72)2511Hay/0	involves: FVB/N	MGI:5298846
cx8	Htt^tm1Hay/Htt^tm1Hay Tg(YAC18)18Hay/0	involves: FVB/N	MGI:5298848
cx9	Htt^tm1Hay/Htt^tm1Hay Tg(YAC46)668Hay/0	involves: FVB/N	MGI:5298849

Genotype
MGI:3586835

hm1

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay
• Genetic Background: involves: C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:25941 )

• most die at around E7.5 and E8.5 and all are dead at E9.5

embryonic lethality between implantation and placentation, incomplete penetrance ( J:25941 )

• most die at around E7.5 and E8.5 and all are dead at E9.5

embryo

abnormal gastrulation ( J:25941 )

• gastrulation is disturbed

embryonic growth arrest ( J:25941 )

• E8.5 embryos fail to neurulate, which leads to disorganization of embryos

decreased embryo size ( J:25941 )

• embryos are small and underdeveloped at E7.5

abnormal extraembryonic tissue morphology ( J:25941 )

• extraembryonic membranes are fragmented at E7.5 and a connection between the allanotis and the placenta does not form

growth/size/body

decreased embryo size ( J:25941 )

• embryos are small and underdeveloped at E7.5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Huntington's disease	DOID:12858	OMIM:143100	J:25941

Genotype
MGI:3586839

ht2

• Allelic Composition: Htt^tm1Hay/Htt⁺
• Genetic Background: involves: C57BL/6J

behavior/neurological

abnormal learning/memory/conditioning ( J:25941 )

• significantly slower to find the hidden platform when it was moved to a new location in the reverse trial of the Morris water maze test, indicating cognitive defects associated with acquiring or using new information in the face of exisiting information

hyperactivity ( J:25941 )

• significantly more active throughout both light- and dark-phases when placed in a novel photocell cage than controls

hyperresponsive ( J:25941 )

• more reactive to handling than controls

nervous system

abnormal globus pallidus morphology ( J:25941 )

• fewer neurons in the globus pallidus, however the caudate/putamen, cerebral cortex, and corpus callosum were normal

abnormal subthalamic nucleus morphology ( J:25941 )

• subthalamic nucleus is decreased in size and volume and contains fewer neurons

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:25941

Genotype
MGI:5617271

cx3

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(HTT*97Q)IXwy/0; Tg(YAC18)18Hay/Tg(YAC18)18Hay
• Genetic Background: FVB.Cg-Htt^tm1Hay Tg(HTT*97Q)IXwy Tg(YAC18)18Hay

behavior/neurological

abnormal motor learning ( J:191147 )

• 2 month old mice exhibit increased falls and decreased latency to fall during rotarod training, indicating a motor learning deficit

• males show an overall greater impairment on the rotarod than males homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

abnormal object recognition memory ( J:191147 )

• at 9 months of age, mice show deficits in object recognition by preference for an unknown object

impaired spatial learning ( J:191147 )

• at 6 and 9 months of age, mice show a spatial deficit in spatial learning by preference for a known object in a novel location

abnormal depression-related behavior ( J:191147 )

• mice spend more time being immobile and less time swimming in the Porsolt forced swim test compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased depressive-like behavior

increased thigmotaxis ( J:191147 )

• during open-field exploration, mice enter the center of the field less frequently and spend less total time in the center of the field compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

• in the elevated plus maze, mice spend less time in the open arms and dip their head off the edges of the open arms less frequently than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay, indicating increased anxiety

abnormal motor capabilities/coordination/movement ( J:191147 )

• during a spontaneous climbing test, 2 month old mice trend toward an increased latency to begin climbing and decreased number of climbing events and spend significantly less time climbing than mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

impaired coordination ( J:191147 )

• in longitudinal rotarod testing, mice exhibit declining performance with age

increased stereotypic behavior ( J:191147 )

• mice show increased stereotypy, or repetitive movement, and decreased jumping compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• however, no difference in distance traveled or ambulation time is seen during spontaneous activity

growth/size/body

increased body weight ( J:191147 )

• increase in body weight compared to wild-type controls and a small increase in body weight compared to mice homozygous for Tg(YAC18)18Hay and Htt^tm1Hay

• body weight gain is greater in females than in males

nervous system

abnormal forebrain morphology ( J:191147 )

• mice show a trend towards reduced forebrain weight at 12 months of age

abnormal corpus callosum morphology ( J:191147 )

• mice show a trend toward reduced corpus callosum volume at 12 months of age

abnormal striatum morphology ( J:191147 )

• mice show reductions in both striatal volume and cortical volume at 12 months of age

abnormal action potential ( J:215223 )

• at 9 months of age, striatal spiny projection neurons show a significant depolarization of the resting membrane potential and elevated action potential threshold, however excitability of these neurons is similar to controls

• action potential threshold of striatal spiny projection neurons is already increased at 6 months of age

impaired synaptic plasticity ( J:215223 )

• mice exhibit progressive hippocampal synaptic plasticity deficit

abnormal CNS synaptic transmission ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit small changes in membrane properties

decreased excitatory postsynaptic current amplitude ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

decreased excitatory postsynaptic current frequency ( J:215223 )

• at 9 months of age, striatal spiny projection neurons exhibit lower frequency of spontaneous excitatory postsynaptic currents (sEPSCs)

• however, release probability from presynaptic terminals is unaltered

reduced long-term potentiation ( J:215223 )

• mice exhibit a deficiency in long-term potentiation at CA3-to-CA1 synapses at 9 months of age but not at 3 months of age

decreased paired-pulse facilitation ( J:215223 )

• paired-pulse facilitation in the hippocampus is reduced at 9 months of age indicating impaired short-term plasticity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:191147 , J:215223

Genotype
MGI:3711011

cx4

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(YAC128)53Hay/0
• Genetic Background: involves: C57BL/6J * FVB

mortality/aging

mortality/aging ( J:120991 )

N • expression of the transgene rescues the embryonic lethality observed in Hdh-null animals

Genotype
MGI:3711010

cx5

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(YAC353G6)W7Hay/0
• Genetic Background: involves: C57BL/6J * FVB/NJ

mortality/aging

mortality/aging ( J:120991 )

N • expression of the transgene rescues the embryonic lethality observed in Hdh-null animals

Genotype
MGI:5298845

cx6

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(YAC72)2511Hay/0
• Genetic Background: involves: FVB/N

mortality/aging

mortality/aging ( J:67366 )

N • embryonic lethality observed in Htt^tm1Hay homozygotes is rescued

reproductive system

reproductive system phenotype ( J:67366 )

♀N • female mice are fertile

oligozoospermia ( J:67366 )

♂ • at 4 months

abnormal spermatid morphology ( J:67366 )

♂ • degenerating

multinucleated giant male germ cells ( J:67366 )

♂ • testes contain giant multinucleated cells and protein aggregates

abnormal male germ cell apoptosis ( J:67366 )

♂

testicular atrophy ( J:67366 )

♂

male infertility ( J:67366 )

♂

cellular

oligozoospermia ( J:67366 )

♂ • at 4 months

abnormal spermatid morphology ( J:67366 )

♂ • degenerating

multinucleated giant male germ cells ( J:67366 )

♂ • testes contain giant multinucleated cells and protein aggregates

abnormal male germ cell apoptosis ( J:67366 )

♂

endocrine/exocrine glands

testicular atrophy ( J:67366 )

♂

Genotype
MGI:5298846

cx7

• Allelic Composition: Htt^tm1Hay/Htt⁺; Tg(YAC72)2511Hay/0
• Genetic Background: involves: FVB/N

reproductive system

testicular atrophy ( J:67366 )

♂ • in some mice

endocrine/exocrine glands

testicular atrophy ( J:67366 )

♂ • in some mice

Genotype
MGI:5298848

cx8

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(YAC18)18Hay/0
• Genetic Background: involves: FVB/N

mortality/aging

mortality/aging ( J:67366 )

N • embryonic lethality observed in Htt^tm1Hay homozygotes is rescued

reproductive system

reproductive system phenotype ( J:67366 )

N • mice exhibit normal testes and are fertile

Genotype
MGI:5298849

cx9

• Allelic Composition: Htt^tm1Hay/Htt^tm1Hay; Tg(YAC46)668Hay/0
• Genetic Background: involves: FVB/N

mortality/aging

mortality/aging ( J:67366 )

N • embryonic lethality observed in Htt^tm1Hay homozygotes is rescued

reproductive system

reproductive system phenotype ( J:67366 )

N • female mice are fertile

male infertility ( J:67366 )

♂