Expression of a dominant-negative type II transforming growth factor β (TGF-β) receptor in the epidermis of transgenic mice blocks TGF-β-mediated growth inhibition
| Autor: | Xiaojing Wang, Donnie S. Bundman, Thomas Krieg, Rik Derynck, Dennis R. Roop, Aibo Jiang, David A. Greenhalgh, Jackie R. Bickenbach |
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| Jazyk: | angličtina |
| Rok vydání: | 1997 |
| Předmět: |
Genetically modified mouse
Keratinocytes Male medicine.medical_specialty Transgene Genes myc Mice Inbred Strains Mice Transgenic Biology Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-myc chemistry.chemical_compound Epitopes Mice In vivo Transforming Growth Factor beta Internal medicine Skin Physiological Phenomena medicine Mitotic Index Animals Humans Amino Acid Sequence Receptor Cells Cultured Skin Mice Inbred ICR Multidisciplinary Epidermis (botany) Receptor Transforming Growth Factor-beta Type II Heterozygote advantage Hypertrophy Keratosis Biological Sciences Molecular biology Skin Aging Endocrinology chemistry Animals Newborn Female Growth inhibition Epidermis Receptors Transforming Growth Factor beta Cell Division Transforming growth factor |
| Popis: | To determine whether a functional type II receptor of transforming growth factor β (TGF-β) is required to mediate the growth inhibitory effect of TGF-β on the skin in vivo , we have generated transgenic mice that overexpress a dominant negative-type II TGF-β receptor (ΔβRII) in the epidermis. The ΔβRII mice exhibited a thickened and wrinkled skin, and histologically the epidermis was markedly hyperplastic and hyperkeratotic. In vivo labeling with BrdUrd showed a 2.5-fold increase in the labeling index over controls, with labeled nuclei occurring in both basal and suprabasal cells of transgenic epidermis. In heterozygotes, this skin phenotype gradually diminished, and by 10–14 days after birth the transgenic mice were indistinguishable from their normal siblings. However, when F 1 mice were mated to homozygosity, perinatal lethality occurred due to the severe hyperkeratotic phenotype, which restricted movement. Cultured primary keratinocytes from ΔβRII mice also exhibited an increased rate of growth in comparison with nontransgenic controls, and were resistant to TGF-β-induced growth inhibition. These data document the role of the type II TGF-β receptor in mediating TGF-β-induced growth inhibition of the epidermis in vivo and in maintenance of epidermal homeostasis. |
| Databáze: | OpenAIRE |
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