RESUMO
We have used the mouse mammary tumor virus promoter to express two dominant negative (DN) fibroblast growth factor receptor (FGFR) isoforms in the mammary epithelium of transgenic mice. While expression of DN-FGFR1(IIIc) showed no discernible phenotype, a similar kinase negative form of FGFR2(IIIb) caused a marked impairment of lobuloalveolar development. The growth retardation was apparent by mid-pregnancy and persisted in the post-partum glands. Despite the substantial underdevelopment of the mammary gland there was a measurable lactational response, but it was insufficient to properly sustain the new-born pups. These findings demonstrate that fibroblast growth factor signalling is necessary for pregnancy dependent lobuloalveolar development of the mammary gland.
Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Receptores Proteína Tirosina Quinases/fisiologia , Receptores de Fatores de Crescimento de Fibroblastos/fisiologia , Transdução de Sinais , Animais , Caseínas/genética , Feminino , Expressão Gênica , Vírus do Tumor Mamário do Camundongo/genética , Camundongos , Camundongos Transgênicos , Proteínas do Leite/química , Fenótipo , Gravidez , Regiões Promotoras Genéticas , Proteínas/análise , RNA/análise , RNA Mensageiro/análise , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/genética , TransgenesRESUMO
Silica fibres from the inflorescence bracts of the grass Phalaris canariensis L. cause dermatitis, and have been implicated in the aetiology of oesophageal cancer in northeastern Iran. Here we describe a method for labelling these fibres so that they can be located in mammalian tissue. Fluorescein was covalently linked to isolated, purified fibres with the silane coupling agent 3-aminopropyl triethoxysilane. The labelled hairs were then rubbed into the backs of mice. These were later killed and their skin fixed, stained and sliced at a thickness of 250 microns. A confocal laser scanning microscope gave brilliant images of the fibres at any depth up to 100 microns or more beneath the surface of the slice. Fibres penetrated deeply into the dermis. Several cubic millimetres of tissue could be surveyed in 1 h. The number of fibres present was approximately 2 mm-3 initially, falling to 0.1 mm-3 after 7 days.