Recombinant inbreeding in mice reveals thresholds in embryonic corpus callosum development

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.

Ephrin-B1 regulates axon guidance by reverse signaling through a PDZ-dependent mechanism

“…Ephrin-B1 null mutant mice on a mixed C57BL/6J.129S4 genetic background did not display ACC (n = 3), and similarly, ephrin-B1 DV F1 C57BL/6J.129S4 mice displayed a well-formed CC (n = 3) ( Table 1). A predisposition toward spontaneous defects of the CC has been documented for some 129 inbred strains; however, we never observed spontaneous ACC in any ephrin-B1 wt mice in the 129S4 inbred genetic background that we used for this study (n = 16) ( Table 1; Wahlsten et al 2006). Considering this genetic background dependence, we characterized the timing of formation of the CC in 129S4 mice.…”

Joubert syndrome: neuroimaging findings in 110 patients in correlation with cognitive function and genetic cause

“…The Sonic hedgehog pathway is critical for the development of the prosencephalon, which is essential for normal formation of the corpus callosum; failure of an established telencephalic midline to fuse results in loss of substrate through which callosal axons can pass 36 37. Pathogenic variants in KIF7 cause JS38 39 as well as acrocallosal syndrome 40–42.…”

Predictability and randomness of paw choices are critical elements in the behavioural plasticity of mouse paw preference

“…Also, we hypothesize that the small differences in maximum predictability and in number of previous reaches to achieve maximum predictability between 9XCA and BTBR mice in both test sessions are the result of minor background genetic differences between them that also regulate the learning and memory system in paw preference behaviour. In any event, the obvious qualitative difference in long-term memory of paw preference learning behaviour may be a useful screening tool to functionally assess mice for potential intercerebral commissural deficiencies (Bohlen, Bailoo, Jordan, & Wahlsten, 2012;Wahlsten, Bishop, & Ozaki, 2006;Wahlsten et al, 2003).…”