Shiverer jimpy double mutant mice. IV. Five combinations of allelic mutations produce three morphological phenotypes.

Mice which simultaneously express mutant genes at both the shi and jp loci (double mutant mice) have phenotypes much more complex than simple addition of individual mutant characteristics. Morphological study of shi jpmsd, shimld jp, and shi/shimld jp, and comparison with previously studied shi jp and shimld jpmsd, shows that 3 classes of central nervous system (CNS) white matter morphology are produced. (1) shi jp shows suppression of most jp characteristics: it is like shi except for more major dense line, and possibly more myelin, than shi alone. No other combination has as much myelin or any major dense line at all. (2) shi jpmsd has qualitative and quantitative characteristics intermediate between the two single mutants. (3) All combinations studied involving shimld have much less myelin than either single mutant. Qualitatively they express most jp locus features but suppress all shi locus features except abnormalities of myelin compaction. The difference between shi and shimld has more influence on the double mutant morphology than the difference between jp and jpmsd. In the 3-mutant combination, shi/shimld jp, the influence of shimld completely overrides that of shi. These morphological phenotypes resist assignment to any hierarchy of normalcy, and their specific features have no simple explanation in presently known molecular biology of the shi and jp locus mutations. They suggest the possibility of multiple copies and multiple primary functions of the messages at these loci.