ACTIN MESSENGER-RNA ISOFORMS ARE DIFFERENTIALLY SORTED IN NORMAL OSTEOBLASTS AND SORTING IS ALTERED IN OSTEOBLASTS FROM A SKELETAL MUTATIONIN THE RAT

Actin isoform sorting has been shown to occur in a variety of cell typ es in culture. To this list we add osteoblasts, in which we show by in situ hybridization that beta-actin is distributed primarily in cell p rocesses and on one side of the nucleus and gamma-actin has a perinucl ear distribution. Osteoblasts from the skeletal mutation toothless (tl ), evaluated under identical conditions, fail to sort these actin isof orms differentially and exhibit diffuse labeling as their major manife station. Northern analyses of actin mRNAs showed no differences betwee n normal and mutant cultures. Shortened osteoblast life span and an in ability to direct osteoclast-mediated bone resorption have recently be en demonstrated in tl mutants. The present results suggest that a fail ure of osteoblasts to sort actin mRNAs may be related to one or both o f these pathological manifestations in this mutation and represent, to our knowledge, the first correlation of an actin mRNA-sorting abnorma lity with a mammalian disease.