Phenotypes associated with this allele

• Allele Symbol: Htt^tm1Szi
• Allele Name: targeted mutation 1, Scott Zeitlin
• Allele ID: MGI:1857722
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Htt^tm1Szi/Htt^tm1Szi	either: (involves: 129/Sv * C57BL/6J) or (involves: 129/Sv * MF1)	MGI:2176436
cn2	Htt^tm1Szi/Htt^tm2Szi Tg(Camk2a-cre)1Szi/0	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * CBA	MGI:3605769
cn3	Htt^tm1Szi/Htt^tm2Szi Tg(Camk2a-cre)2Szi/0	involves: 129S/SvEv * 129S1/Sv * C57BL/6 * CBA	MGI:3605770
cx4	Hap1^tm1Id/Hap1^tm1Id Htt^tm1Szi/Htt^tm1Szi	involves: 129S/SvEv * 129S1/Sv * C57BL/6	MGI:3521639
cx5	Hap1^tm1Id/Hap1^+ Htt^tm1Szi/Htt^tm1Szi	involves: 129S/SvEv * 129S1/Sv * C57BL/6	MGI:3521640
cx6	Htt^tm1Szi/Htt^tm1Szi Tg(HTT*)BXwy/0	involves: 129S/SvEv * FVB	MGI:4438240
cx7	Htt^tm1Szi/Htt^tm1Szi Tg(HTT*)1Xwy/0	involves: 129S/SvEv * FVB	MGI:4438242

Genotype
MGI:2176436

hm1

• Allelic Composition: Htt^tm1Szi/Htt^tm1Szi
• Genetic Background: either: (involves: 129/Sv * C57BL/6J) or (involves: 129/Sv * MF1)

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

mortality/aging

embryonic lethality, complete penetrance ( J:29267 )

• die between E8.5 and E10.5

embryo

increased embryonic tissue cell apoptosis ( J:29267 )

• E7.5 embryos exhibit an increase in apoptotic cells

increased embryonic epiblast cell apoptosis ( J:29267 )

• epiblast contains numerous pyknotic nuclei

embryonic growth arrest ( J:29267 )

• at E8.5, embryos appear underdeveloped and have not progressed beyond the E7.5 egg cylinder stage, however E6.5 embryos are indistinguishable from wild-type

abnormal embryonic tissue morphology ( J:29267 )

abnormal egg cylinder morphology ( J:29267 )

• egg cylinders are smaller and stubby at E7.5

decreased egg cylinder size ( J:29267 )

• egg cylinders are smaller at E7.5

disorganized embryonic tissue ( J:29267 )

• despite the formation of the three germ layers, embryos do not expand normally, are disorganized, and exhibit dense, amorphous masses of cells in some areas

abnormal extraembryonic tissue morphology ( J:29267 )

abnormal amniotic cavity morphology ( J:29267 )

• at E8.5, the amniotic cavity often contains dead cells with pyknotic nuclei

small amniotic cavity ( J:29267 )

• at E8.5, the amniotic cavity is small

abnormal Reichert's membrane morphology ( J:29267 )

• thicker Reichert's membrane that exhibits many interspersed nodules covered with clusters of parietal cells

increased Reichert's membrane thickness ( J:29267 )

disorganized extraembryonic tissue ( J:29267 )

• extraembryonic portion of the E7.5 embryo appears folded and disorganized

abnormal visceral endoderm morphology ( J:29267 )

• the surface of the visceral endoderm consists of semi-spherical blebs due to numerous invaginations

cellular

increased embryonic tissue cell apoptosis ( J:29267 )

• E7.5 embryos exhibit an increase in apoptotic cells

increased embryonic epiblast cell apoptosis ( J:29267 )

• epiblast contains numerous pyknotic nuclei

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	Huntington's disease	DOID:12858	OMIM:143100	J:29267

Genotype
MGI:3605769

cn2

• Allelic Composition: Htt^tm1Szi/Htt^tm2Szi; Tg(Camk2a-cre)1Szi/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * CBA

mortality/aging

premature death ( J:65520 )

• die between 11 and 13 months of age

growth/size/body

decreased body size ( J:65520 )

• smaller than controls at weaning and at P60

behavior/neurological

limb grasping ( J:65520 )

• abnormal limb clasping at P60 that becomes progressively more severe such that mice curl their body upon clasping and maintain the posture for several seconds following return to cage

tremors ( J:65520 )

• exhibit a slight tremor at 10-12 months of age

impaired coordination ( J:65520 )

• exhibit motor defects in mutants subjected to cage-top rotation test and elevated wire rod hanging test

decreased locomotor activity ( J:65520 )

• noticeably hypoactive at 10-12 months of age

nervous system

gliosis ( J:65520 )

• gliosis is seen throughout the forebrain in older mutants

astrocytosis ( J:65520 )

• reactive astocytosis in the entorhinal cortex, striatum, and frontal cortex at 4 and 10 months of age

neurodegeneration ( J:65520 )

• 4 and 8 month old mutants exhibit neurodegeneration in the external capsule fibre tracts and in fibre bundles of the internal capsule within the striatum, in the amygdala and in both the frontal and dorsal cortex

reproductive system

oligozoospermia ( J:65520 )

♂ • exhibit a reduction in the number of spermatocytes and round spermatids in the seminiferous tubules and in mature motile sperm in the lumen of the epididymis

abnormal seminiferous tubule morphology ( J:65520 )

♂ • disorganized and contain fewer spermatocytes and round spermatids compared to controls

small testis ( J:65520 )

♂ • testis is about 50% the weight of controls

reduced male fertility ( J:65520 )

♂

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:65520 )

♂ • disorganized and contain fewer spermatocytes and round spermatids compared to controls

small testis ( J:65520 )

♂ • testis is about 50% the weight of controls

cellular

oligozoospermia ( J:65520 )

♂ • exhibit a reduction in the number of spermatocytes and round spermatids in the seminiferous tubules and in mature motile sperm in the lumen of the epididymis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:65520

Genotype
MGI:3605770

cn3

• Allelic Composition: Htt^tm1Szi/Htt^tm2Szi; Tg(Camk2a-cre)2Szi/0
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6 * CBA

mortality/aging

premature death ( J:65520 )

• mutants that are hydrocephalic die by P35

• none survive longer than 13 months

growth/size/body

decreased body size ( J:65520 )

• smaller than controls at weaning and at P60

behavior/neurological

limb grasping ( J:65520 )

• abnormal limb clasping at P21 that becomes progressively more severe such that mice curl their body upon clasping and maintain the posture for several seconds following return to cage

tremors ( J:65520 )

• exhibit a slight tremor at 10-12 months of age

impaired coordination ( J:65520 )

• exhibit motor defects in mutants subjected to cage-top rotation test and elevated wire rod hanging test

decreased locomotor activity ( J:65520 )

• noticeably hypoactive at 10-12 months of age

nervous system

hydrocephaly ( J:65520 )

• about 8% are hydrocephalic by P10

abnormal brain internal capsule morphology ( J:65520 )

abnormal striatum morphology ( J:65520 )

• striatum is disorganized at 8-months of age

abnormal cerebral cortex morphology ( J:65520 )

• cortex is disorganized at 8-months of age

gliosis ( J:65520 )

• gliosis is seen throughout the forebrain in young mutants

astrocytosis ( J:65520 )

• reactive astocytosis in the entorhinal cortex, striatum, and frontal cortex at 4 and 8 months of age

neurodegeneration ( J:65520 )

• neurodegeneration in the caudal/lateral region of the cortex at 4-6 months of age and in the rostral and caudal portions of the brain adjacent to the external capsule and in the entorhinal cortex at 8 months of age

• exhibit shrunken eosinophilic neurons, indicative of neuronal damage, in the hippocampus at 8-months of age

• 8 month old mutants exhibit neurodegeneration in the external capsule fibre tracts and in fibre bundles of the internal capsule within the striatum, in the amygdala and in both the frontal and dorsal cortex

• degeneration is essentially complete by 10 months

reproductive system

oligozoospermia ( J:65520 )

♂ • exhibit a reduction in the number of spermatocytes and round spermatids in the seminiferous tubules and in mature motile sperm in the lumen of the epididymis

abnormal seminiferous tubule morphology ( J:65520 )

♂ • disorganized and contain fewer spermatocytes and round spermatids compared to controls

small testis ( J:65520 )

♂ • testis is about 50% the weight of controls

reduced male fertility ( J:65520 )

♂

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:65520 )

♂ • disorganized and contain fewer spermatocytes and round spermatids compared to controls

small testis ( J:65520 )

♂ • testis is about 50% the weight of controls

cellular

oligozoospermia ( J:65520 )

♂ • exhibit a reduction in the number of spermatocytes and round spermatids in the seminiferous tubules and in mature motile sperm in the lumen of the epididymis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Huntington's disease		DOID:12858	OMIM:143100	J:65520

Genotype
MGI:3521639

cx4

• Allelic Composition: Hap1^tm1Id/Hap1^tm1Id; Htt^tm1Szi/Htt^tm1Szi
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6

embryo

decreased embryo size ( J:94581 )

• at E8.5 the embryonic portion of the conceptus is smaller than normal similar to Hdh^tm1Szi single homozygotes

absent neural folds ( J:94581 )

• at E8.5 neural folds are absent similar to Hdh^tm1Szi single homozygotes

absent somites ( J:94581 )

• at E8.5 somites are absent similar to Hdh^tm1Szi single homozygotes

growth/size/body

decreased embryo size ( J:94581 )

• at E8.5 the embryonic portion of the conceptus is smaller than normal similar to Hdh^tm1Szi single homozygotes

Genotype
MGI:3521640

cx5

• Allelic Composition: Hap1^tm1Id/Hap1⁺; Htt^tm1Szi/Htt^tm1Szi
• Genetic Background: involves: 129S/SvEv * 129S1/Sv * C57BL/6

embryo

decreased embryo size ( J:94581 )

• at E8.5 the embryonic portion of the conceptus is smaller than normal similar to Hdh^tm1Szi single homozygotes

absent neural folds ( J:94581 )

• at E8.5 neural folds are absent similar to Hdh^tm1Szi single homozygotes

absent somites ( J:94581 )

• at E8.5 somites are absent similar to Hdh^tm1Szi single homozygotes

growth/size/body

decreased embryo size ( J:94581 )

• at E8.5 the embryonic portion of the conceptus is smaller than normal similar to Hdh^tm1Szi single homozygotes

Genotype
MGI:4438240

cx6

• Allelic Composition: Htt^tm1Szi/Htt^tm1Szi; Tg(HTT*)BXwy/0
• Genetic Background: involves: 129S/SvEv * FVB

mortality/aging

mortality/aging ( J:157723 )

N • mice are born at Mendelian ratios

nervous system

nervous system phenotype ( J:157723 )

N • unlike Htt^tm1Szi homozygotes, mice do not exhibit neurodegeneration or increased anxiety-related response

Genotype
MGI:4438242

cx7

• Allelic Composition: Htt^tm1Szi/Htt^tm1Szi; Tg(HTT*)1Xwy/0
• Genetic Background: involves: 129S/SvEv * FVB

mortality/aging

mortality/aging ( J:157723 )

N • mice are born at Mendelian ratios