Regional distribution of myelin basic protein in the central nervous system of quaking, jimpy, and normal mice during development and aging

摘要

AbstractMyelin basic protein (MBP) was quantified using a RIA technique in the spinal cord, cerebellum, diencephalon plus brainstem region and cerebral hemispheres of two dysmyelinating murine mutants, quaking (qk) and jimpy (jp) mice. Comparison was made with normal control values. The whole life‐span has been investigated: ie, ages ranging from 0 to 26 days for the jp, 0 to one year for the qk, and prenatal stage to three years for the control animals. Assays in the mutants at early ages were rendered feasible by the use of marker genes, which has allowed the diagnosis of the mutation at birth, 12 days before the expression of their typical tremor phenotype. Special care was given to the period of early myelinogenesis in order to clarify the dysynchrony between the various parts of the central nervous system.In normal mice, MBP was already detected in the brain of 19‐day‐old embryos. During development, rapid accumulation of MBP first occurred in the spinal cord then in the diencephalon, the brainstem, the cerebellum, and finally in the cerebral hemispheres.In the 25‐day‐old jimpy mutant, levels of MBP were found dramatically decreased, never exceeding 6 of the normal controls in any of the areas investigated.The situation for the quaking mouse was quite different. This mutant could be investigated up to one year old. At that age, a high discrepancy was observed between the values found in the brain and in the spinal cord (respectively, 10 and 35) compared to normal controls.In both mutants, not only were the levels of MBP decreased, but also its appearance during development was delayed. Nevertheless, in both mutants the caudo‐rostral timing of myelination as assayed by MBP levels was maintained. Furthermore, the later myelination occurred, the stronger was the deficit in MBP. Interestingly, in the quaking mutant, the specific plasticity of the spinal cord was exemplified by its ability to reduce constantly, even at an advanced age, its initial def