Influence of Genetic Strain Background on the Magnitude of Behavioral Recovery Observed in Weaver Mutant Mice Following Bilateral Intrastriatal Grafting of Mesencephalic Cell Suspensions

The weaver (wv) mutation leads to loss of mesencephalic (DA) cells in the homozygous state. Behaviorally, weaver mutants display tremor, gait instability and toppling over to the sides after a few steps. Cell suspensions were prepared from the ventral mesencephalic flex-ure of El2 normal mouse embryos by mild en-zymatic digestion (collagenase/dispase) and implanted bilaterally into the striata of weaver mutants to counteract the genetically-induced mesostriatal DA deficiency. Wild-type mice (+/+), non-operated weaver mutants, and weaver mutants with bilateral grafts were tested in a battery of spontaneous behavioral tasks to determine recovery of functional responses. All the experiments were conducted in mice of the three conditions (normal, weaver, grafted weaver) maintained on two genetic strain backgrounds: a C57BL/6J-AW4/A 4 x CBA/ CaGnLe-A/A hybrid strain (referred to as B6CBA-AW4/A), and a B6CBA-AW4/A x BALB/ cJ hybrid strain (referred to as BC4). The following behavioral parameters were analyzed: (1) as an index of equilibrium, the time interval between placement on and falling off a balance rod suspended over the ground; (2) as an index of locomotor coordination, the number of times animals toppled over to the sides during a 5-min observation period; as indices of exploratory activity (3), the number of times animals crossed over squares in a 25-square open-field matrix and (4) the number of times animals stood on their hind-limbs to scan the environment (rearings). Repeated-measures analyses of variance were carried out with two grouping factors, condition and strain, and one repeated-measures factor, trials. Appropriate transformations (in reciprocal or square-root scale) were introduced to remove existing correlations between means and standard deviations in the cells of the design, which would otherwise violate the assumptions required for validity of the F-tests in the analyses of variance.