The 2.2-kb promoter of cartilage-derived retinoic acid-sensitive protein controls gene expression in cartilage and embryonic mammary buds of transgenic mice

Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted pr otein primarily expressed in chondrocytes. Pathologically, CD-RAP is detect ed in melanoma, chondrosarcoma and breast cancer. As an approach to define the transcriptional regulatory domains responsible for induction of chondro cyte activity in vivo, we generated transgenic mice harboring various fragm ents of the mouse CD-RAP promoter linked to the Escherichia coli beta -gala ctosidase gene. Analysis of the transgene expression pattern by X-gal stain ing indicates that 2251 bp of the CD-RAP 5'-flanking sequence generates bet a -galactosidase activity in all cartilage in embryos and adult animals. In addition, we also detected transient X-gal staining in mammary gland primo rdium from day 11.5 to 15.5 of gestation. Histological examination revealed that the transgene is located in the chondrocytes of cartilage and the epi thelial cells of mammary buds. The cartilage transgene expression pattern i s consistent with that of endogenous CD-RAP gene expression. The presence o f beta -galactosidase in the mammary buds led us to the demonstration of a unique pattern of transient endogenous expression of CD-RAP in the mammary bud. The finding of transient CD-RAP expression in mammary buds suggests th at it may play a role in the organogenesis of mammary glands. (C) 2000 Publ ished by Elsevier Science B.V./International Society of Matrix Biology.