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 (<em>Fdxr</em>) 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 (<em>Otop2</em>) 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. 

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.

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B6;129S-Fdxr<m1J> Otop2<m1J>/GrsrJ Frozen Embryos