Mice homozygous for the stumbler spontaneous mutation (stu) have clinical features suggesting a cerebellar defect. They can be recognized at 12 days of age by a stumbling locomotion characterized by a high-stepping broad-based gait. Homozygous mutant mice become less active with age and progressively smaller than their normal sibs and usually die before weaning. There are fewer than normal Purkinje cells and granule cells from about 10 days of age onward and a consequent smaller size of the cerebellum. The Purkinje cells have small dendritic arborizations and immature spines on their somata. They also have an increased number of mitochondrial profiles both in cell bodies and in swellings on dendrites. The morphology of the granule cells appears normal.
The stumbler mutation (stu) arose spontaneously at The Jackson Laboratory in 1975 in the inbred strain C3H/HeJ. It was sibling bred to F32 and was then backcrossed for 2 generations, via backcross-intercross, to C3HeB/FeJ-a/a using ovarian transplantation from homozygous females. To improve breeding performance, the mutation was then backcrossed via ovary transplant into B6C3F1-Aw-J host females mated to C57BL/6J males, followed by intercross of the heterozygous offspring. The strain was continually maintained in this manner of backcross-intercross to C57BL/6J until it was crypreserved in 1992 from matings of C57BL/6J females with heterozygous males at generation N5.
Homozygous mutant animals die by 18 days on this background (C57BL/6).
When using the stumbler mouse strain in a publication, please cite the originating article(s) and include JAX stock #001772 in your Materials and Methods section.