Weaver mutant mice are characterized by a decrease in striatal dopamine (DA), which is associated with a progressive loss of DA neurones in the substantia nigra. This mutant thus provides the opportunity to examine the functional effects of DA neurones grafted to the striatum in a genetic model of parkinsonism. Ventral mesencephalic tissue from normal foetuses was placed on the surface of the right dorsal striatum of adult weaver mutants. After grafting, animals were tested for methamphetamine-induced circling behaviour. Mutants with DA containing grafts displayed a significant circling bias toward the left, non-grafted side. Mutants without grafts did not display any rotational bias to either side. These results demonstrate that grafted DA containing neurones establish a functional innervation of the weaver striatum and suggest that grafting of neural tissue is a viable approach in restoring function in genetic degenerative disorders of the nigrostriatal system.
Bibliographical noteFunding Information:
We thankD r. C.D. Nordschowa ndDr. B. Sample of the Departmenotf Pathologyfo r supporta ndfor providingm ethamphetaminCe.J;. Alyea and R. Funkhousero f the Departmenot f Pathologyf or technicahl elp;G. Buckleyo f the Departmenotf Pa-thologya ndJ . Demmao f the Departmenotf Medical Illustrationfso r skillful assistancwe ith graphicsa nd photographyT.h is work was supportedin part by NIH GrantN S14426( B.G.).
- Functional recovery
- Nigral transplant
- Parkinson disease
- Rotational behavior
- Weaver mutant mouse