MORPHOLOGICAL ABNORMALITIES IN THE HIPPOCAMPUS OF THE WEAVER MUTANT MOUSE

The lamination of the hippocampus in the homozygous B6CBA weaver mouse (wv/wu) was compared with that in normal B6CBA littermates (+/+) and C57BL/6J mice using Nissl and Timm's staining. In Nissl-stained prepar ations, the normal littermates exhibit a compact, regular arrangement of pyramidal cells in area CA3 of the hippocampus. In contrast, in hom ozygous weaver mutant mice, the pyramidal cell layer of area CA3 frequ ently appears to be thicker than normal with an apparent increase of n europil, as evidenced by the presence of cell-free spaces within the l ayer. Also, small ectopic clusters of pyramidal cells and sometimes th e subdivision of the pyramidal cell layer into 2 or 3 layers were foun d throughout the dorsoventral extent of the hippocampus. In Timm's sta ined preparations of the normal mouse hippocampus, two clearly separat ed bundles of axons were seen emerging from the hilus: one bundle runn ing above the pyramidal cell layer of area CA3 (i.e., the suprapyramid al messy fiber layer, SPMFL), and the second bundle running below the pyramidal cell layer (i.e., the infrapyramidal messy fiber layer, IPMF L). In contrast, in some homozygous weaver mice, the origin of the mes sy fiber bundles is clearly different from normal; specifically, messy fibers emerge in a diffuse fashion from the area between suprapyramid al and infrapyramidal messy fiber layers. In other weaver mice, short, discontinuous bundles diverge from the infrapyramidal messy fiber lay er and invade the thickened pyramidal cell layer. In addition, ectopic pyramidal cells are situated below the IPMFL in area CA3. The morphol ogical changes observed in hippocampus of weaver mutants are likely to be secondary to a more basic genetic defect.