The porcine calcitonin receptor promoter directs expression of a linked reporter gene in a tissue and developmental specific manner in transgenic mice.
We have investigated the transcriptional regulation of the porcine calcitonin (CT) receptor (pCTR) promoter in transgenic mice. A construct containing 2.1 kb pCTR 5' flanking region, fused to a beta-galactosidase (lacZ) gene, was employed for the production of transgenic mice. At 11.5 days of development lacZ expression was observed in the embryonic brain and spinal cord. By 15.5 days post fertilization, lacZ expression was detected in the developing mammary gland, external ear, cartilage primordium of the humerus, and anterior naris (nostril). RT-PCR on RNA from these fetal tissues showed endogenous mouse CTR (mCTR) expression. In neonatal and adult transgenics, lacZ expression was silenced, except in brain, spinal cord, and testis (adults only). Endogenous mCTR gene expression and pCTR promoter activity were corepressed in the same tissues from adult mice. No pCTR promoter activity was detected in the kidney or bone of transgenic animals. This suggests that additional DNA sequences may be required for pCTR promoter activity in these tissues. From these results, we conclude that the pCTR promoter is active only in tissues expressing endogenous mCTR. Many of the these tissues represent previously unknown sites of CTR gene expression. Finally, the developmental regulation of pCTR/mCTR in tissues such as breast and cartilage primordium suggests that CTRs may play a role in the morphogenesis of these tissues.
Jagger
C
C
Department of Histopathology, St. George's Hospital Medical School, London, United Kingdom.
Gallagher
A
A
Chambers
T
T
Pondel
M
M
D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D018003:Receptors, Calcitonin / Q000235:genetics* / Q000502:physiology*; D013552:Swine
D018003:Receptors, Calcitonin