Biomaterial Database

Targeted expression of the dominant-negative prolactin receptor in the mammary gland of transgenic mice results in impaired lactation. 2003

Elise Saunier, and Fariel Dif, and Paul A Kelly, and Marc Edery

Institut National de la Santé et de la Recherche Médicale, Unité 344, Endocrinologie Moléculaire, Faculté de Médecine Necker, 75730 Paris, France.

The F3-short form of the rat PRL receptor (F3-SPRLR) form acts as a dominant negative inhibitor in vitro. We have developed a transgenic mouse model in which the rat F3-SPRLR was expressed in mammary epithelium under the control of the mouse mammary tumor virus promoter. Two lines of mice were characterized and shown to express the transgene in the mammary gland. No developmental abnormalities or differences from wild-type littermates were observed on the basis of size, activity, or fertility. Mice with a low level of transgene expression had a mammary phenotype similar to the wild type. However, mice overexpressing the transgene (levels much higher than those of the endogenous long PRLR transcript) had impaired mammary gland differentiation and lactation. In these mice, whole-mount and histological analyses demonstrated normal ductal development, but severely reduced lobuloalveolar outgrowth. signal transducer and activator of transcription-5 phosphorylation and expression of beta-casein and whey acidic protein gene were decreased. In vivo bromodeoxyuridine incorporation at midpregnancy showed that the reduction in mammary development was not due to an inhibition of ductal growth and side-branching. This model demonstrates for the first time in vivo a function of the SPRLR and a local and targeted effect of PRL on the mammary gland that are essential for its function, but not for its development.

UI	MeSH Term	Description	Entries
D007775	Lactation Disorders	Disturbances of MILK secretion in either SEX, not necessarily related to PREGNANCY.	Hypogalactia,Disorder, Lactation,Disorders, Lactation,Hypogalactias,Lactation Disorder
D008321	Mammary Glands, Animal	MAMMARY GLANDS in the non-human MAMMALS.	Mammae,Udder,Animal Mammary Glands,Animal Mammary Gland,Mammary Gland, Animal,Udders
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D008894	Milk Proteins	The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)	Milk Protein,Protein, Milk,Proteins, Milk
D010641	Phenotype	The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.	Phenotypes
D011981	Receptors, Prolactin	Labile proteins on or in prolactin-sensitive cells that bind prolactin initiating the cells' physiological response to that hormone. Mammary casein synthesis is one of the responses. The receptors are also found in placenta, liver, testes, kidneys, ovaries, and other organs and bind and respond to certain other hormones and their analogs and antagonists. This receptor is related to the growth hormone receptor.	Prolactin Receptors,PRL Receptors,Prolactin Receptor,Receptors, PRL,Receptor, Prolactin
D002455	Cell Division	The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.	M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005260	Female		Females