A novel behavioral method to detect motoneuron disease in Wobbler mice aged three to seven days old.

The Wobbler mouse possesses an inherited autosomal recessive form of motoneuron disease. The most characteristic abnormality is the degeneration of motoneurons, mostly in the cervical spinal cord, and in the brain stem cranial motor nuclei. The underlying pathology shows up as symptoms that are only detectable confidently around the time of weaning (age 3 weeks). We now report a new method designed to identify presymptomatic Wobbler mice by behavioral and statistical approaches. We measured body weight, righting reflex (RR) and gender to examine whether these parameters have an impact on the status of the disease before age 3 weeks. Using a total of 341 NFR/wr strain pups, we found a strong association between RR and the Wobbler disease status (p<0.0001) between postnatal days 3 to 7, and achieved greater than 97% correct classification of Wobblers. Therefore the measurement of RR allows the early detection of the affected Wobbler (wr/wr) mice with a minimum of error. This method has been used in our laboratory for immunocytochemical studies that show the early sprouting of immunoreactive serotonin and peptidergic fibers in the cervical spinal ventral horn by postnatal days 7 and 12 respectively. The early detection of Wobbler mice thus facilitates significant new understanding regarding the pathogenesis of motoneuron disease. We can now examine potentially therapeutic approaches which may be more effective than when administered in the symptomatic weanlings (work in progress).