Rostrocaudal gradient of transgene expression in adult skeletal muscle

Abstract

Transgenic mice were produced in which expression of the reporter gene chloramphenicol acetyltransferase (CAT) is controlled by regulatory elements of a rodent myosin light chain gene. CAT activity was readily detectable in muscles of these mice but negligible in a variety of nonmuscle tissues. Unexpectedly, levels of CAT expression varied greater than 100-fold from muscle to muscle, forming a gradient in which a muscle's position in the rostrocaudal axis was correlated with its level of CAT enzyme activity and abundance of CAT mRNA. Thus, rostral muscles (innervated by cranial nerves) had the lowest levels of CAT, thoracic muscles had intermediate levels, and caudal muscles (innervated through lumbar and sacral roots) had the highest levels. We established that myosin light chain sequences are responsible for the gradient of CAT expression but observed no strong gradient of endogenous myosin light chain expression. We argue that elements that are silent or masked by other sequences in their native context are revealed in the transgene and that the rostrocaudal gradient of gene expression they produce reveals the existence of a positionally graded endogenous regulator of gene expression. These transgenic mice provide evidence that cells in adult mammals retain "positional information" of a sort hitherto studied largely in embryos. The transgene they express may provide a means for determining how such positional values are generated and maintained.