The mode of inheritance of a defect in lamination in the hippocampus of BALB/c mice.

In BALB/c mice the lamination of the pyramidal cell layer of area CA3c of the hippocampus is abnormal in that early-generated neurons are superficial and late-generated neurons are deep. To determine the mode of inheritance of this strain difference, the laminar distribution of mossy fibers and hippocampal pyramidal cells was examined using the Timm's sulfide silver method in BALB/c x C57BL/6 F1 and F2 hybrids, in BALB/cByJ and C57BL/6J mice which were fostered to females of the other strain before receiving their first meal, and in the CXB series of recombinant inbred strains (originally derived using BALB/c and C57BL/6 as progenitor strains). The pattern of hippocampal lamination was classified as "BALB/c-like" if pyramidal cells were present below an intrapyramidal mossy fiber layer or as "B6-like" if only an infrapyramidal mossy fiber layer was present. In both male and female CB6F1 and B6CF1 hybrids the distribution of mossy fibers is BALB/c-like. In 7 of 9 F2 hybrids the distribution was BALB/c-like and in the remaining 2 B6-like. In the cross-fostered mice the pattern was always the same as normally raised mice of the same genotype. Of the recombinant inbred strains, 5 (CXBD, CXBG, CXBH, CXBI, and CXBK) had BALB/c-like hippocampal lamination and 2 (CXBE and CXBJ) had B6-like lamination. These results are consistent with inheritance by means of a single autosomal dominant (or semi-dominant) gene. The provisional name "Hippocampal lamination defect" and gene symbol Hld are suggested. The Hld mutation is only the third known neurological mutation in mice which apparently affects neuronal migration, and the fact that it affects only a single subdivision of the hippocampus indicates that Hld may be a useful tool for future studies of the development of the central nervous system and particularly of the cell biology of neuronal migration and neuronal specificity.