RESTRICTED EXPRESSION OF MOV13 MUTANT ALPHA-1(I) COLLAGEN GENE IN OSTEOBLASTS AND ITS CONSEQUENCES FOR BONE-DEVELOPMENT

Cell type-specific differences in the transcriptional control of the m ouse gene coding for the al chain of collagen type I (Collal) have bee n revealed previously with the help of the Movl3 mouse strain which ca rries a retroviral insert in the first intron of the gene. Transcripti on of this mutant Collal allele is completely blocked in all mesoderma l cell types tested so far, with the exception of the odontoblast wher e it is expressed at an apparently normal rate (Kratochwil et al. [198 9] Cell 57:807-816). To define the tissue specificity of the mutant al lele more precisely, we have now studied its expression in osteoblasts , another skeletogenic cell type which, like odontoblasts, produces hi gh amounts of collagen I. Evidence for transcription of the Mov13 alle le was obtained by in situ hybridization in homozygous (M/M) and heter ozygous (M/+) bone tissue, in grafts as well as in vivo. The presence of mouse collagen I and the development of bone tissue were demonstrat ed in M/M skeletal elements grown on the chick chorioallantoic membran e (CAM). Further support for expression of the mutant gene was obtaine d from two 16 day M/M fetuses in vivo. Bone tissue of diverse embryolo gical origin (vertebrae and ribs of semitic origin, long bones derived from lateral plate, calvariae from head paraxial mesoderm, and mandib ulae from head neural crest) expresses the mutant allele. However, in situ hybridization experiments indicate that only a subpopulation of o steoblasts is capable of transcribing it at a high rate, resulting in severe impairment of bone development in grafts and in vivo. Therefore , osteoblasts, in comparison to odontoblasts and fibroblast-like cells , assume an intermediate position with respect to transcription of the Movl3 allele. We suggest that this diversity in the utilization of th e mutant collagen gene reflects cell type-specific differences in the transcriptional regulation of the wild type (wt) Collal gene. (C) 1993 Wiley-Liss, Inc.