Changes in brain components during the development of mice homozygous for the locus ?dwarf? (dw)1,5

Abstract

Brain composition and developmental changes were investigated in mice homozygous for the locus "dwarf," and characterized by a reduced level of growth hormone, thyroid stimulating hormone, and prolactin, and by secondary hypothyroidism. The difference in adult brain weight (-32%) between the dwarf and the normal mice was not found to parallel the difference in body weight (-71%), whereas the differences in the weight of the liver (-79%) and that of the kidney (-75%) did. Several biochemical parameters of brain development were assayed in dwarf and normal mice between the ages of 15 and 210 days. Levels of cerebrosides, sulfatides, gangliosides, phospholipids, cholesterol, protein, and RNA (per gram wet weight) were the same for the dwarf and the controls, but the net difference in total brain DNA was less than the net total brain RNA difference (-11% vs. -27%). Total brain lipids (absolute quantities) were the same at 15 days. The difference was -37% by the 50th day, and remained constant thereafter. No change in the specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase or 3'-phosphoadenosine-5'-phosphosulfate: galactocerebroside sulfotransferase was observed. These data suggest that the regulation of the development of brain structures is maintained, but the level of the synthesis of the various brain constituents is reduced in proportion to the brain weight. The development of the dwarf brain seems to proceed harmoniously.