Prevention of congenital otolith defect in pallid mutant mice by manganese supplementation.

HERE are numerous genetic loci in mice which affect primarily pigmenta‘tion; SEARLE (1968) lists 44 loci with nearly 100 mutations. Eighteen (40%) of these loci possess mutant alleles with known pleiotropic effects. In some cases the pleiotropic effect has been traced to a biochemical, morphological, or developmental phenomenon, but no direct relationship has been demonstrated between the mutation’s effect on pigmentation and the associated defect. The investigations presented in this paper suggest that some of these pleiotropic effects may involve subtle relationships between pigmentation and trace-element requirements. The gene used in these studies is pallid (symbolized by pa) which was discovered in a wild population of mice (ROBERTS 1931). I t was first identified as pink-eyed-2 because it was similar to but phenotypically and genetically distinct from pink-eyed dilution. In addition to the effect of pa on pigmentation, CASTLE (1941) observed that the viability of pa mice was considerably reduced under crowded conditions, and that they “tended to be nervous and jumpy.” LYON ( 195 1 ) showed that specific behavioral anomalies of these mice were associated with otolith defects within the inner ear. As a result of these studies and of LYON’S (1953, I954,1955a, 1955b) more detailed examination of pa, it can be described as a color mutation with pleiotropic effects on behavior, growth, and viability. The effect on pigmentation (including the absence of pigment from the membranous labyrinth) is fully penetrant in the homozygote recessive (pa/pa) whereas the effect on otolith formation is highly variable. Although the mass of otolith crystals (otoconia) may be reduced in or absent from any of the four otoliths, there is considerable asymmetry between left and right ears and between the utricle and saccule of the same ear. LYON (1954) elegantly demonstrated a significant effect of litter size on the penetrance of the otolith defect. She therefore postulated that the otolith defect “may be due to competition [in utero] for food substances, either general o r particular, o r for oxygen, space, etc.”