Tg(HDexon1)62Gpb Transgene Detail MGI Mouse (MGI:2386951)

Tg(HDexon1)62Gpb
Transgene Detail

Nomenclature

Symbol:	Tg(HDexon1)62Gpb
Name:	transgene insertion 62, Gillian Bates
MGI ID:	MGI:2386951
Synonyms:	R6/2, Tg(HDexon1)62nGpb
Transgene:	Tg(HDexon1)62Gpb Location: unknown

Transgene
origin

Strain of Origin:

CBA x C57BL/6

Transgene
description

Transgene Type:	Transgenic (random, expressed)
Mutation:	Insertion
	A human HD fragment containing a polyglutamine-repeat expansion was isolated from a clone derived from a patient with Huntington's disease. The transgene contained approximately 1 kb of 5' UTR region, exon 1 which initially contained 142 CAG repeats, and 262 bp of intron 1 followed by a neomycin cassette. Subsequent analysis showed that the number of CAG repeats was prone to increase when inherited through the male line due to instability in the germline. A range of 141 to 157 was observed. On a background that involves C57BL/6 and CBA, transgneic mice have been obseved to carry >(CAG)200 repeat expansions. The transgene is ubiquitously expressed. (J:36689)

Find Mice (IMSR)

Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)

Carrying this Mutation:

Mouse Strains: 2 strains available Cell Lines: 0 lines available

Phenotype
summary

Phenotype Summary by Mammalian Phenotype terms

(show or hide all annotated terms)

Genotypes are listed in the next section.

Key:

hm	homozygous	ht	heterozygous
cn	conditional genotype	cx	complex: > 1 genome feature
tg	involves transgenes	ot	other: hemizygous, indeterminate,...
N	normal phenotype		expected model not found

Affected Systems	Genotypes:	tg1	tg2	tg3	tg4	tg5	tg6
behavior/neurological		√			√	√
limb grasping		√			√
abnormal voluntary movement		√
tremors					√
impaired balance					√
stereotypic behavior					√
abnormal vocalization					√
seizures					√
impaired coordination						√
		tg1	tg2	tg3	tg4	tg5	tg6
cardiovascular system		√
abnormal myocardial fiber morphology		√
decreased heart weight		√
dilated heart left ventricle		√
decreased cardiac output		√
abnormal cardiac stroke volume		√
abnormal diastolic filling velocity		√
decreased ventricle muscle contractility		√
decreased left ventricle systolic pressure		√
		tg1	tg2	tg3	tg4	tg5	tg6
digestive/alimentary system					√
abnormal pancreatic alpha cell morphology					√
abnormal pancreatic beta cell morphology					√
decreased pancreatic beta cell number					√
abnormal pancreatic delta cell morphology					√
		tg1	tg2	tg3	tg4	tg5	tg6
endocrine/exocrine glands					√
abnormal pancreatic alpha cell morphology					√
abnormal pancreatic beta cell morphology					√
decreased pancreatic beta cell number					√
abnormal pancreatic delta cell morphology					√
small ovary					√
small seminal vesicle					√
small testis					√
		tg1	tg2	tg3	tg4	tg5	tg6
growth/size		√	√		√
decreased body weight			√		√
postnatal slow weight gain		√
weight loss		√			√
		tg1	tg2	tg3	tg4	tg5	tg6
homeostasis/metabolism					√
abnormal glucose homeostasis					√
decreased circulating insulin level					√
impaired glucose tolerance					√
		tg1	tg2	tg3	tg4	tg5	tg6
life span/aging					√	√
premature death					√
extended life span						√
		tg1	tg2	tg3	tg4	tg5	tg6
muscle		√
abnormal myocardial fiber morphology		√
decreased ventricle muscle contractility		√
		tg1	tg2	tg3	tg4	tg5	tg6
nervous system		√	√		√	√	√
abnormal striatum morphology		√	√			√	√
abnormal cerebral cortex morphology		√	√			√	√
abnormal cerebellum morphology		√
abnormal nervous system physiology		√
abnormal neuron physiology		√
seizures					√
abnormal neuron morphology			√
neuronal intranuclear inclusions			√
decreased brain size					√
decreased brain weight			√
		tg1	tg2	tg3	tg4	tg5	tg6
renal/urinary system					√
polyuria					√
		tg1	tg2	tg3	tg4	tg5	tg6
reproductive system					√
small seminal vesicle					√
small testis					√
abnormal female reproductive system morphology					√
small ovary					√
small uterus					√
female infertility					√
		tg1	tg2	tg3	tg4	tg5	tg6
vision/eye				√
abnormal eye morphology				√

		tg1	tg2	tg3	tg4	tg5	tg6
Disease Models		√	√		√
Huntington Disease; HD		√	√		√

Phenotypic
data by
genotype

Phenotypic Data by Genotype

(show or hide all phenotypic details)

Genotype

Allelic Composition

Genetic Background

tg1 Disease Model

Tg(HDexon1)62Gpb/0

B6CBA-Tg(HDexon1)62Gpb/1J

tg2 Disease Model

Tg(HDexon1)62Gpb/0

involves: C57BL/6 * CBA

tg3

Tg(HDexon1)62Gpb/0

involves: C57BL/6 * CBA/J * SJL

tg4 Disease Model

Tg(HDexon1)62Gpb/0

involves: C57BL/6J * CBA/J

tg5

Tg(HDexon1)62Gpb/0
Tgm2^tm1.1Rmgr/Tgm2^tm1.1Rmgr

involves: 129X1/SvJ * C57BL/6 * CBA

tg6

Tg(HDexon1)62Gpb/0
Tgm2^tm1.1Rmgr/Tgm2⁺

involves: 129X1/SvJ * C57BL/6 * CBA

Disease
models

Mouse Models of Human Disease	Note	Genotype			Ref(s)
Mouse Models of Human Disease	Note		Allelic Composition	Genetic Background	Ref(s)
Models involving transgenes or other mutation types.¹
Huntington Disease; HD OMIM ID: 143100		tg1	Tg(HDexon1)62Gpb/0	B6CBA-Tg(HDexon1)62Gpb/1J	J:111237, J:99425
		tg4	Tg(HDexon1)62Gpb/0	involves: C57BL/6J * CBA/J	J:36689
		tg2	Tg(HDexon1)62Gpb/0	involves: C57BL/6 * CBA	J:42085

¹Models involving transgenes or other mutation types may also appear in other sections of the table.

Notes

Transgenic mice exhibit a progressive neurological phenotype that mimics many of the features of HD. Onset of phenotype is apparent from approximately 8 weeks of age based on home cage behavior. Some functional tests indicate the presence of a motor impairment from 5-6 weeks and cognitive impairment from 3 weeks. Epileptic seizures are seen in a small percentage of transgenic mice. A failure to gain weight is more pronounced in males than females. Immunohistochemistry with antibodies raised against the N-terminus of huntingtin reveals aggregates in the form of intranuclear inclusions and neuropil aggregates.

Transgenic mice on a background that involves C57BL/6 and CBA display a progressive neurological phenotype that mimics many of the features of Huntington Disease in humans, including choreiform-like movements, involuntary stereotypic movements, tremor, and epileptic seizures, as well as nonmovement disorder components, including unusual vocalization. Frequent urination, loss of body weight and muscle bulk occurs through the course of the disease. Neurological developments include Neuronal Intranuclear Inclusions (NII), which contain both the huntingtin and ubiquitin proteins (NII have subsequently been identified in human HD patients); the onset of HD symptoms occurs between 9 and 11 weeks.

References

Original:	J:36689 Mangiarini L et al., "Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice." Cell 1996 Nov 1;87(3):493-506
All:	134 reference(s)

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
Citing These Resources Funding Information Warranty Disclaimer & Copyright Notice Send questions and comments to User Support.	last database update 11/20/2009 MGI_4.31 Web browser compatibility