Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although homozygotes are viable and fertile, few pups born to homozygous females survive. The Donating Investigator maintains the C57BL/6 congenic strain using heterozygous crosses. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of cerebrum, cerebellum, spinal cord, heart, lung, kidney, liver, spleen, thymus, uterus, prostate, and ovary. Homozygotes exhibit a quivering or shaking phenotype and are more easily startled by sound, hence the "skittish" nickname designation. The tremor is without ataxia. Homozygotes exhibit hyperactivity. Although growth rate and food consumption are similar to wildtype controls, homozygotes have a reduced body weight. The observed hyperactivity and reduced body weight is more significant in female homozygotes. Ultrastructural analysis of myelin sheath in cerebrum and spinal cord reveals increased myelin sheath thickness in the spinal cord and defective myelin compaction (membrane periodicity) in both spinal cord and cerebrum. An increased number of mitochondria is observed by ultrastructural analysis of sciatic nerve.
When crossed with TRAMP transgenic mice (Stock No. 003135) the double mutant mice, 20-25 weeks in age, exhibit no detectable metastases, while 38% of wild-type littermates carrying the TRAMP transgene alone developed metastases in the lung and/or lymph nodes.
