TIME OF INITIATION AND SITE OF ACTION OF THE MOUSE CHROMOSOME-11 IMPRINTING EFFECTS

Previous studies have shown that mice with paternal disomy for chromos ome 11 are consistently larger at birth than their normal sibs, wherea s mice with the maternal disomy are consistently smaller. An imprintin g effect with monoallelic expression of some gene/s affecting growth w as indicated. Here we show that the size differences become establishe d prior to birth and are only maintained subsequently, indicating that the gene repression is limited to prenatal development. Fetal analysi s was limited to 12.5-17.5 days post coitum. However by extrapolating the data backwards it could be calculated that both the maternal and p aternal size effects might commence as early as 7 days post coitum, al though possibly slightly later. It may be deduced that initiation of e xpression of the gene/s responsible may occur at about this time in de velopment. The two disomy growth rates were mirror-images of each othe r, suggesting that expressed gene dosage is the underlying cause. Diff erential growth of the placentas of the two disomies was also found, a nd extrapolation of these data backwards suggested that the placental size differences were initiated later in development than those for th e fetuses. The differential placental growth of the maternal and pater nal disomies may therefore have developed independently or emerged as a consequence of the differential fetal growth. In either event it wou ld seem that the expression of the responsible gene occurs in the fetu s itself to cause the anomalies of growth. The data therefore provide information on the temporal and tissue specificity of the gene/s respo nsible for the chromosome 11 imprinting effects. Possible candidate ge nes are discussed.