Recombinant Inbreeding in Mice Reveals Thresholds in Embryonic Corpus Callosum Development

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Douglas Wahlsten, Visiting Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: The inbred strains BALB/cWah1 and 129P1/ReJ both show incomplete penetrance for absent corpus callosum (CC); about 14% of adult mice have no CC at all. Their F1 hybrid offspring are normal, which proves that the strains differ at two or more loci pertinent to absent CC. Twenty-three recombinant inbred lines were bred from the F2 cross of BALB/c and 129, and several of these expressed a novel and severe phenotype after only three or four generations of inbreeding – total absence of the CC and severe reduction of the hippocampal commissure (HC) in every adult animal. As inbreeding progressed, intermediate sizes of the CC and the HC remained quite rare. This striking phenotypic distribution in adults arose from developmental thresholds in the embryo. CC axons normally cross to the opposite hemisphere via a tissue bridge in the septal region at midline, where the HC forms before CC axons arrive. The primary defect in callosal agenesis in the BALB/c and 129 strains is severe retardation of fusion of the hemispheres in the septal region, and failure to form a CC is secondary to this defect. The putative CC axons arrive at midline at the correct time and place in all groups, but in certain genotypes, the bridge is not yet present. The relative timing of axon growth and delay of the septal bridge create a narrow critical period for forming a normal brain.

Additional Information

Genes, Brain and Behavior, 5: 170-188.
Language: English
Date: 2006
Complementation test, Corpus callosum, Critical period, Hippocampal commissure, Incomplete penetrance, Recombinant inbred strains

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