PRLR Gene Editing    

Prolactin (PRL) is a pleiotropic neurohormone (~200 amino acids [aa]) that is secreted by the mammal pituitary gland into the bloodstream, reaching peripheral tissues and organs beyond the brain. PRL acts through dimerization with PRL receptor (PRLR) resulting in a signaling cascade that modulates essential mammalian behaviors (e. g., social recognition, parental care, and learning) and promotes important changes in the female reproductive tissues and organs. PRLR is a member of the class I cytokine receptor family, comprising a transmembrane domain (TM), an extracellular domain (ECD), and an intracellular domain (ICD), which is activated after dimerization with PRL and affected by other ligands, such as the growth hormone (GH). In humans, PRLR is located on chromosome 5, on chromosome 15 in mice and was mapped to chromosome 16 in pigs. The PRLR gene is expressed in many tissues, for example in ovaries, testes, deferent ducts, kidneys, oviduct, and small and large intestine and also in the hypothalamus.

The expressed product of the PRLR gene is a receptor protein- a single transmembrane protein belonging to class I of the cytokine receptor superfamily, which includes interleukins, growth hormone receptor (GHR), granulocyte colony stimulating factor, granulocyte macrophage colony-stimulating factor, erythropoietin, thrombopoietin, oncostatin M, gp130, leukemia inhibiting factor (LIF), ciliary neurotrophic factor and leptin receptor (LEPR). So far, four PRLR forms have been identified, three of which are membrane isoforms (short, intermediate and long) and the fourth has a soluble form and contains the extracellular domain only. These membrane isoforms are composed of a ligand-binding extracellular domain, an intracellular catalytic domain, and a transmembrane domain. The long PRLR form is the most common. The expression of different prolactin receptor forms depends on female reproductive status and cell type. The different isoforms differ in the amount and amino acid composition of the receptor’s cytoplasmic portion.

PRLRs are involved in a negative feedback mechanism that regulates prolactin secretion, which is tonically inhibited by dopamine released from TIDA neurons of the hypothalamic arcuate nucleus which act on dopamine D2 receptors on the pituitary gland. Therefore, prolactin binds to PRLRs on the TIDA neurons that leads to an increase in dopamine secretion, thereby reducing prolactin secretion by the pituitary. This mechanism is supported by the study of mice lacking the dopamine D2 receptor, which is hyperprolactinaemic due to loss of dopaminergic inhibition at the pituitary gland. Interestingly, PRLR has also been reported to be expressed on lactotrophs of the pituitary gland where it may provide an autocrine loop to regulate lactotroph function. In addition, human and rodent studies have reported roles for the PRLR in the reproduction and development of breast and prostate tumors.

In addition to its well-known functions in reproductive processes, PRLR is also related to glucose homeostasis, as glucose levels are higher in Prlr knock-out mice after glucose injection. PRLR regulates glucose levels indirectly by modulating the secretion of insulin through changes in islet density, β-cell number, and mass. Consistent with these results, knocking down PRLR expression decreases glucose-induced insulin secretion in islets isolated from rats.

PRLR Gene Editing Services

CRISPR/Cas9 Platform^CB at Creative Biogene is dedicated to offering comprehensive CRISPR/Cas9 gene editing services and products for academic research, biotech research and pharmaceutical drug discovery. With deep gene editing knowledge and extensive experience in experimental operation and data processing, we help you effectively control PRLR genes knockout/knockin/point mutation in cells or animals via CRISPR/Cas9 technology.

Service	Details	Alternative cell lines or animal species
PRLR Gene Editing Cell Line Generation	gRNA design and synthesis Transfect the cell lines you're interested Select the high expression cells and sort monoclonal cell Validate the knockout/knockin/point mutation of PRLR by PCR and sequencing Provide cryogenically preserved vials of stable cells and final reports	HEK239T, Hela, HepG2, U87, Ba/F3, CHO, MDA-MB-453, MDA-MB-231NIH3T3, T47D, Neuro2a, MCF7, RKO, K562, RAW264.7, etc.
PRLR Gene Editing Animal Model Generation	PRLR gene conventional knockout animals PRLR gene conditional knockout animals PRLR point mutation animals PRLR knockin animals	Mouse, rat, rabbit, zebrafish, C. elegans, etc.

Related Products at CRISPR/Cas9 Platform^CB