Transplanted transgenically marked oligodendrocytes survive, migrate and myelinate in the normal mouse brain as they do in the shiverer mouse brain.
The dye Hoechst 33342 was combined with an immunodetectable transgene product (chloramphenicol acetyltransferase, CAT) expressed in differentiated oligodendrocytes to trace their fate after transplantation in the normal and the shiverer mouse brain. In the shiverer brain, the technique allowed us to visualize grafted cells inside myelin basic protein-positive myelin patches. Most of these cells were CAT-positive/Hoechst 33342-negative, reinforcing our hypothesis that cell division probably follows migration of grafted oligodendrocytes. Correlation of their morphology and distribution with their location in the host CNS suggested a local effect on the cell division and morphogenesis of the grafted material. When compared with transplantation of fragments of normal newborn donor tissue into the newborn shiverer brain, no difference could be seen between the behaviour of normal and transgenic oligodendrocytes. In the normal brain, transgenic oligodendrocytes survived at least 150 days and successfully myelinated the host axons. The timing of differentiation of grafted cells was similar in both types of recipient brains. Migration occurred rostrally and caudally. Although migrating cells could be observed along the meninges and the blood vessels, migration occurred preferentially along white matter tracts. The extent of migration was influenced by the site of implantation, and grafted cells could be found up to 6 mm from the grafting point. No differences in the timing of differentiation or the pattern or extent of migration could thus be demonstrated when transgenic oligodendrocytes were transplanted in the normal or the shiverer brain. This validates our previous studies using the newborn shiverer mouse as recipient.
Lachapelle
F
F
U 134 INSERM, Hôpital de la Salpétrière, Paris, France.
Duhamel-Clerin
E
E
Gansmüller
A
A
Baron-Van Evercooren
A
A
Villarroya
H
H
Gumpel
M
M
D000818:Animals; D000831:Animals, Newborn; D001562:Benzimidazoles; D015415:Biomarkers; D001921:Brain / Q000473:pathology*; D001931:Brain Mapping; D016380:Brain Tissue Transplantation; D002465:Cell Movement; D015500:Chloramphenicol O-Acetyltransferase / Q000032:analysis; D006085:Graft Survival; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000033:anatomy & histology*; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology / Q000637:transplantation*; D011993:Recombinant Fusion Proteins / Q000032:analysis
D001562:Benzimidazoles; D015415:Biomarkers; D011993:Recombinant Fusion Proteins; D015500:Chloramphenicol O-Acetyltransferase; C017807:bisbenzimide ethoxide trihydrochloride