Abnormal perikaryal accumulation of neurofilament light protein in the brain of mice transgenic for the human protein: sequence of postnatal development.
Adult mice transgenic for the human form of neurofilament light protein display abnormal perikaryal immunoreactivity for this protein in many regions of the CNS and notably the thalamus. To determine the sequence of development of these anomalies, we have compared normal and transgenic mice of different postnatal ages (P0-P70), using immunocytochemistry with primary antibodies recognizing both murine and human sequence of neurofilament light protein (NR-4) or the human form only (DP5-1-12). In normal mouse brainstem, several nuclei displayed immunoreactive perikarya at P0. The number of these perikarya culminated at P10, followed by a general decrease, some nuclei having lost all perikaryal immunostaining in adults. In transgenic mouse brainstem, the distribution of perikaryal immunoreactivity already resembled at P0 that of P10 in normal mouse, and remained unchanged in adults. Differences between normal and transgenic mice were even more pronounced in the forebrain. Some nuclei of normal mouse basal forebrain that were weakly immunopositive at P10 or P20, but no longer in adults, were already labeled at P0 and remained so or became more intense at later stages in transgenic mice. In the thalamus of normal mouse, perikaryal labeling was faint, confined to a few nuclei, and detected only transiently at P10, whereas in transgenics, it was already observed in some nuclei at P0, increased in intensity and extended to other nuclei at P10, and persisted thereafter. Strongly immunoreactive, inflated perikarya with excentric nuclei were prominent in these thalamic nuclei at P20, and even larger in size at P70. In the cerebral cortex of normal mice, layers II-III and layer V of many cytoarchitectonic areas showed immunoreactive cell bodies at P10, a distribution which became gradually restricted to the parietal cortex in adults. In transgenic mice, immunopositive cortical cell bodies were first detected at P3, filled layers II-III of numerous cortical areas at P10, and then rapidly decreased in number to approach the adult pattern at P20. In the cortex as well as thalamus of P10 transgenic mice, differences between the patterns of cellular staining with clones NR4 and DP5-1-12 antibodies indicated that both the murine and human proteins were accumulated in these neurons. Thus, neurofilament light protein accumulation in the transgenic mouse brain generally involved neurons displaying perikaryal immunoreactivity for the protein at least at some point during normal postnatal development.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D000911:Antibodies, Monoclonal; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D001933:Brain Stem / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002531:Cerebellum / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology; D016900:Neurofilament Proteins / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016900:Neurofilament Proteins; C044882:neurofilament protein L