Sensitivity patterns for the induction of homeotic shifts in a favorable strain of mice.

Abstract

In an effort to develop a prescreening system that is sensitive, is compatible with in-vivo administration of presumptive teratogens, and utilizes morphological endpoints, we are studying the induction of homeotic shifts in the axial skeleton. Our earlier work had demonstrated the existence of critical periods for certain such shifts, even though the (C57BL x NB)F1 hybrid used was not entirely suitable for this purpose. Using 100 R X-rays on successive days during the period of major organogenesis, we have now analyzed the sensitivity pattern of the BALB/c, since this strain normally straddles thresholds for the position of axial borders. Mortality, birthweight, and skeletal anomalies were analyzed, in addition to the homeotic shifts. --Day 9 1/4 postconception was clearly the most sensitive stage for the production of posterior shifts at the thoraco-lumbar border and the lumbo-sacral border, and for increases in the number of sternebrae and costo-sternal junctions. Anterior shift could be induced three days later, on day 12 1/4, but this was confined to only one of the four characters, the thoraco-lumbar border. There are a number of indications that, at given stages during the study period, BALB/c embryos correspond developmentally to chronologically somewhat earlier stages of two strains studied previously. The present results do not support the hypothesis that factors influencing the quantitative skeletal characters act by way of body size. --Since homeotic shifts can be produced by a number of mechanisms and are obvious indications that developmental interference has occurred, and since such shifts are easy to score and convenient to analyze quantitatively, our identification of a highly suitable strain and of stages of maximum sensitivity in this strain should aid in making the system useful in the prescreening for chemical teratogens.