These Hprt knock-out mice exhibit a form of the HPRT protein that contains a long polyglutamine repeat, and develop a phenotype similar to the human translated CAG repeat disorders.
Dr. Peter J Detloff, University of Alabama at Birmingham
Mutant mice develop a phenotype similar to the human translated CAG repeat disorders showing a late onset neurological phenotype. Mice have handling-induced seizures, weight gain, reduced vertical activity, clasping response, impaired performance on the rotarod task, and premature death. Mice subjected to frequent handling have a median age of death of 45 weeks. There is the presence of neuronal intranuclear inclusions containing at least part of the polyglutamine-containing HPRT protein and ubiquitin. These results indicate that expanded CAG repeats need not be located within one of the classic repeat disorder genes to have a neurotoxic effect. Note that the size of the CAG repeat may not be stable and any reduction in repeat size may lead to a later onset phenotype.
|Allele Name||targeted mutation 1, Peter J Detloff|
|Allele Type||Targeted (Inserted expressed sequence)|
|Allele Synonym(s)||hprt(CAG)146; JO1|
|Gene Symbol and Name||Hprt, hypoxanthine guanine phosphoribosyl transferase|
|Promoter||Hprt, hypoxanthine guanine phosphoribosyl transferase, mouse, laboratory|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A construct was created that introduced a long CAG repeat (n=146 units) into an Xho1 site in exon 3 of a genomic fragment of the locus. An additional 4.9kb genomic fragment, which included exon 4 of the gene, was added to this repeat-containing construct. Appropriately targeted clones had sequences containing the 146-unit CAG repeat, encoding a stretch of 146 glutamines, in place of wild-type exon 3.|
|Mutations Made By|| |
Dr. Peter Detloff, University of Alabama at Birmingham
The Hprt locus is on the X chromosome. Homozygous females can be mated to hemizygous males to maintain the strain. Mice breed well up to 25 - 30 weeks. The expected coat color is black.
When using the JO1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #003138 in your Materials and Methods section.