How to translate text using browser tools
1 March 2004 Expression by Transgenesis of a Constitutively Active Mutant Form of the Prolactin Receptor Induces Premature Abnormal Development of the Mouse Mammary Gland and Lactation Failure
Isabelle Gourdou, Jacqueline Paly, Catherine Hue-Beauvais, Laurence Pessemesse, John Clark, Jean Djiane
Author Affiliations +
Abstract

Prolactin (PRL) initiates signal transduction by inducing homodimerization of PRL receptor (PRL-R). We have previously developed a mutant form of the PRL-R in which a part of the extracellular domain is deleted. This receptor constitutively activates protein gene transcription. We examined the oligomerization of the mutant PRL-R using two differently epitope-tagged receptors in a coimmunoprecipitation assay. It was shown that mutant receptor dimers were formed in a ligand-independent manner, which may explain the constitutive activity on milk protein gene expression. To study the biological activity of this mutant PRL-R on mammary gland development, we generated two lines of transgenic mice expressing the corresponding cDNA specifically in the mammary epithelial cells. For both transgenic lines, the mammary gland of 8-wk-old virgin mice was overdeveloped with numerous dilated ductal and alveolar structures, whereas only a limited duct network was present in wild-type animals at the same age. During pregnancy, the ducts and alveoli of transgenic mice were more developed than those of control animals. At parturition, the transgenic animals failed to lactate and nourish their offspring, and the involution of the mammary gland was strongly delayed. In conclusion, the expression of a constitutively active PRL-R by transgenesis induces a premature and abnormal mammary development and impairs terminal differentiation and milk production at the end of pregnancy.

Isabelle Gourdou, Jacqueline Paly, Catherine Hue-Beauvais, Laurence Pessemesse, John Clark, and Jean Djiane "Expression by Transgenesis of a Constitutively Active Mutant Form of the Prolactin Receptor Induces Premature Abnormal Development of the Mouse Mammary Gland and Lactation Failure," Biology of Reproduction 70(3), 718-728, (1 March 2004). https://doi.org/10.1095/biolreprod.103.019448
Received: 10 June 2003; Accepted: 1 November 2003; Published: 1 March 2004
KEYWORDS
cytokines
early development
mammary glands
mechanisms of hormone action
prolactin receptor
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top