This strain has both an R389Q point mutation in ferredoxin reductase and a point mutation in the 5-prime UTR of otopetrin 2. This spontaneous mutant develops a mature onset stiffening of the hindquarters, mitochondrial defects and retinal ganglion cell degeneration, providing a model for mitochondriopathy with optic atrophy.
Read More +Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous (Hypomorph) | Fdxr | ferredoxin reductase |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous | Otop2 | otopetrin 2 |
The stiffened hindquarters phenotype presents at approximately 9 weeks of age, but has presented as early as 7 weeks of age or as late as almost 12 weeks of age. The hind legs become stiffened and are held much wider than normal and the hips and proximal tail also appear stiffened. The gait becomes rigid and sometimes hop-like in the hindquarters although the front legs appear to move in the normal alternating manner without noticeable stiffness. This stiffening of the hindquarters is progressive, but does not become crippling and homozygotes are able to move reasonably, access the food hopper and water bottle, and reproduce. Both males and females will reproduce after phenotypic onset and homozygous females have taken care of their litters, but homozygous females are not used to maintain this strain. One female homozygote at 6 weeks of age and one female homozygote at five and a half weeks of age, along with aged matched controls, were assessed for their ability to swim and both were able to swim. Two distinct point mutations were identified in the region of Chromosome 11 to which this mutation mapped: a C to T SNV at Chromosome 11 position 115,269,462 bp (GRCm38) resulting in the codon change cGg/cAg in ferredoxin reductase (Fdxr) and the resulting amino acid change R389Q; and a G to A change at Chromosome 11 position 115,332,175 bp (GRCm38) in the 5-prime UTR of otopetrin 2 (Otop2) with unknown consequence. Mitochondriopathy with optic atrophy has been attributed to the ferrodoxin reductase mutation. Ferrodoxin NADP reductase activity is reduced in homozygotes, most severely in muscle and brain but also significantly reduced in liver and heart. Retinal ganglion cell degeneration is evident at 6 months of age when approximately half of the retinal ganglion cell layer nuclei are lost and transmission electron micrographs of these cells show empty cytoplasm, shrunken nuclei, aggregated chromatin, thinned myelin sheaths, and damaged mitochondria in their axons.
The stiffened hindquarters mutation arose spontaneously in the B6;129S-Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze/J colony at The Jackson Laboratory in late 2013. The Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze mutation was removed from this mutant subline by one backcross to C57BL/6J and selective sibling intercrossing thereafter. In 2014 sperm was cryopreserved from homozygous males at generation N1F3.
Allele Name | mutation 1 Jackson |
---|---|
Allele Type | Spontaneous (Hypomorph) |
Allele Synonym(s) | FdxrR389Q; stiff |
Gene Symbol and Name | Fdxr, ferredoxin reductase |
Gene Synonym(s) | |
Strain of Origin | B6;129S-Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze/J |
Chromosome | 11 |
Molecular Note | This spontaneous C-to-T transition at chromosome 11 position 115,269,462 bp (GRCm38) causes a p.R389Q substitution and was identified in the same spontaneous mutant mouse as Otop3m1J. |
Allele Name | mutation 1 Jackson |
---|---|
Allele Type | Spontaneous |
Allele Synonym(s) | Otop3m1J; stiff |
Gene Symbol and Name | Otop2, otopetrin 2 |
Gene Synonym(s) | |
Strain of Origin | B6;129S-Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze/J |
Chromosome | 11 |
Molecular Note | This is a spontaneous G-to-A transition in the 3' UTR in chromosome 11 position 115,332,175 bp (GRCm38) that was identified in the same spontaneous mutant as the Fdxrm1J mutation. |
Although they can reproduce, female homozygotes are not used for breeding. Instead this strain is maintained by intercrossing heterozygous females with either homozygous or heterozygous males.
When using the stiffened hindquarters mouse strain in a publication, please cite the originating article(s) and include JAX stock #026096 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Fdxr, Heterozygous for,Otop3 |
Frozen Mouse Embryo | B6;129S-Fdxr<m1J> Otop2<m1J>/GrsrJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;129S-Fdxr<m1J> Otop2<m1J>/GrsrJ Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;129S-Fdxr<m1J> Otop2<m1J>/GrsrJ Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6;129S-Fdxr<m1J> Otop2<m1J>/GrsrJ Frozen Embryos | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.