Chunk #229 — VIII. A possible underlying neurobiology: connectivity constellations — B. Quality and/or quantity of connections involved in vulnerabilities
Rodent models provide support for quantitative and qualitative effects of variations in connectivity constellation genes. Hints of redundancies in the ways in which these genes might work come from studies of effects of gene × gene interactions in brains of knockout mice. Mice with knockout of the addiction-associated gene NrCAM and another immunoglobulin + fibronectin domain cell adhesion molecule gene, L1, display substantial reductions in brain volume and substantial developmental brain-based phenotypes (NrCAM L1KO). No observable differences between the brains of wildtype mice and knockouts of either NrCAM or L1 alone can be identified, however. While gross brain differences in knockouts of only a few of the “connectivity constellation” genes can be identified, it appears likely that more subtle, more qualitative differences might be induced by variants at many more single loci from this list. Larger quantitative differences that can be grossly observed may require contributions from variants at several of these gene loci.
