HISTOLOGICAL ANALYSIS OF SELECTED BRAIN-REGIONS OF HYPOTRANSFERRINEMIC MICE

This study utilizes a mutant mouse line (Hp) in which an established essential trophic factor, transferrin (Tf), is deficient due to a splicing defect in the processing of Tf precursor mRNA. As this mouse mutant is new to neurological research, the initial stage of the investigation, histological analysis of the brain and spinal cord, is reported here. Using a number of standard histological stains, such as hematoxylin and eosin, luxol fast blue/cresyl violet and silver staining, we see a decrease in the amount of white matter and neurofilament staining and altered neuronal morphology throughout the brain and spinal cord. Regions in which postnatal development is significant such as the hippocampus and cerebellum are particularly affected in this mutant. The cells of the dentate gyrus and Ammon's horn of the hippocampus are smaller, more densely packed and the normal orderly appearance of the CA3 and CA4 regions of Ammon's horn is disrupted. The cerebellum has a decrease in white matter and the molecular, Purkinje cell and granule cell layers all show decreased silver staining for neurofilament and appear less ordered than normal. These results demonstrate that neurohistological alterations exist in the adult hypotransferrinemic mice despite systemic replacement of transferrin. Furthermore, these data suggest certain brain regions are particularly sensitive to disruption in iron delivery. The results of this initial study indicate the Hp animal may be an interesting model for investigating specific aspects of neural development and has considerable potential for examining the importance of iron regulation in the brain.