Basic Information
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Description
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- GNRHR: Receptor for gonadotropin releasing hormone (GnRH) that mediates the action of GnRH to stimulate the secretion of the gonadotropic hormones luteinizing hormone (LH) and follicle- stimulating hormone (FSH). This receptor mediates its action by association with G-proteins that activate a phosphatidylinositol- calcium second messenger system. Isoform 2 may act as an inhibitor of GnRH-R signaling. Defects in GNRHR are a cause of idiopathic hypogonadotropic hypogonadism (IHH). IHH is defined as a deficiency of the pituitary secretion of follicle-stimulating hormone and luteinizing hormone, which results in the impairment of pubertal maturation and of reproductive function. Defects in GNRHR are a cause of fertile eunuch syndrome (FEUNS). Fertile eunuch syndrome is a mild phenotypic form of HH going with the presence of normal testicular size and some degree of spermatogenesis. Belongs to the G-protein coupled receptor 1 family. 2 isoforms of the human protein are produced by alternative splicing.
- Protein type: GPCR, family 1; Membrane protein, integral; Membrane protein, multi-pass; Receptor, GPCR. Chromosomal Location of Human Ortholog: 4q21.2. Cellular Component: membrane; integral to plasma membrane; plasma membrane.
- Molecular Function: gonadotropin-releasing hormone receptor activity; peptide binding. Biological Process: G-protein coupled receptor protein signaling pathway; multicellular organismal development. Disease: Hypogonadotropic Hypogonadism 7 With Or Without Anosmia.
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Targeting strategy
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Gene targeting strategy for B-hGNRHR mice. The exons 1-3 of mouse Gnrhr gene that encode extracellular domain, transmembrane domain, cytoplasmic region and 3’UTR are replaced by human counterparts in B-hGNRHR mice. The promoter and 5’UTR region of the mouse gene are retained. The human GNRHR expression is driven by endogenous mouse GNRHR promoter, while mouse Gnrhr gene transcription and translation will be disrupted.
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mRNA expression analysis in humanized B-hFPR1 mice
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Strain specific analysis of GNRHR mRNA expression in wild-type C57BL/6JNifdc mice and B-hGNRHR mice by RT-PCR. Pituitary RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hGNRHR mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human GNRHR primers. Mouse Gnrhr mRNA was detectable in wild-type. Human GNRHR mRNA was detectable only in homozygous B-hGNRHR mice but not in wild-type mice.
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Protein expression analysis
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Western blot analysis of GNRHR protein expression in homozygous B-hGNRHR mice. Pituitary and testis tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hGNRHR mice (H/H), and then analyzed by western blot with anti-GNRHR antibody (Abcam, ab183079). 40 μg total proteins were loaded for western blotting analysis. GNRHR was detected in pituitary and testis in wild-type mice and homozygous B-hGNRHR mice, as the antibody is cross-recognize both human and mouse GNRHR. (The GnRHR include a 30 kDa GnRHR I variant, a mature 64 kDa variant, a 136 kDa variant.)
