B6CBA-Tg(HDexon1)62Gpb/2J

Stock number: 004601

Description

This strain is discontinued, please refer to strains:
002810 B6CBA-Tg(HDexon1)62Gpb/1J
006494 B6CBA-Tg(HDexon1)62Gpb/3J

Detailed description

This line is transgenic for the 5' end of the human HD gene carrying >(CAG)200 repeat expansions. The CAG repeat is unstable on transmission with a tendency to increase when inherited through the male line. The transgene is ubiquitously expressed. 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. However, the use of appropriate functional tests indicates 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 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. Commonly known as the "R6/2" strain.

Allele

Symbol: Tg(HDexon1)62Gpb
Name: transgene insertion 62, Gillian Bates
MGI accession ID: MGI:2386951
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(HDexon1)62Gpb
Marker name: transgene insertion 62, Gillian Bates
Chromosome: 4
Strain of origin: CBA x C57BL/6
Expressed genes: HTT,huntingtin,human
Molecular note: 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. 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, transgenic mice have been observed to carry >(CAG)200 repeat expansions. The insertion site has been localized to a position on mouse chromosome 4 in an intron of predicted gene GM12695. The transgene is ubiquitously expressed.
General note: 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.