Fibroblast growth factor receptor signalling has a role in lobuloalveolar development of the mammary gland.
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.
Jackson
D
D
Laboratory of Viral Carcinogenesis, Imperial Cancer Research Fund, London, UK.
Bresnick
J
J
Rosewell
I
I
Crafton
T
T
Poulsom
R
R
Stamp
G
G
Dickson
C
C
D000818:Animals; D002364:Caseins / Q000235:genetics; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D015870:Gene Expression; D008321:Mammary Glands, Animal / Q000254:growth & development*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins / Q000737:chemistry; D010641:Phenotype; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000032:analysis; D012313:RNA / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D019076:Transgenes
D002364:Caseins; D008894:Milk Proteins; D011506:Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D012313:RNA; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2