B6-hFOLH1 (hPSMA) Mouse
Product Name
B6-hFOLH1 (hPSMA) Mouse
Product ID
C001779
Strain Name
C57BL/6NCya-Folh1tm1(hFOLH1)/Cya
Backgroud
C57BL/6NCya
Status
When using this mouse strain in a publication, please cite “B6-hFOLH1 (hPSMA) Mouse (Catalog C001779) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
FOLH1
Gene Alias
PSM, FGCP, FOLH, GCP2, PSMA, mGCP, GCPII, NAALAD1
NCBI ID
Chromosome
Chr 11 (Human)
MGI ID
Datasheet
Strain Description
The FOLH1 gene, also known as prostate-specific membrane antigen (PSMA) or glutamate carboxypeptidase II (GCPII), encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. This protein functions as a glutamate carboxypeptidase, acting on various substrates including the nutrient folate (essential for its intestinal absorption) and the neuropeptide N-acetyl-l-aspartyl-l-glutamate (NAAG). In the brain, FOLH1 modulates excitatory neurotransmission by hydrolyzing NAAG, thereby releasing glutamate [1]. It is expressed in a wide range of tissues, including the prostate, central and peripheral nervous systems, kidney, small intestine, liver, and various tumor-associated vasculatures [2]. Aberrant expression of FOLH1 is notably associated with several diseases; it is significantly upregulated in prostate cancer cells and is a crucial diagnostic and prognostic indicator for this malignancy. Additionally, mutations in FOLH1 can lead to impaired intestinal absorption of dietary folates, resulting in low blood folate levels and hyperhomocysteinemia [3]. Its expression in the brain has also been implicated in pathological conditions related to glutamate excitotoxicity, and it is increasingly recognized as a therapeutic target in various solid tumors beyond prostate cancer, such as hepatocellular carcinoma, breast cancer, and Merkel cell carcinoma [2].
The B6-hFOLH1 mouse is a humanized model constructed by replacing aa.45 to partial intron 2 of the mouse Folh1 gene with the human FOLH1 cDNA of the extracellular domain (aa.44~750)-3’UTR of mouse Folh1-WPRE-BGH pA cassette. The murine cytoplasmic-transmembrane domain (aa.1~44) will be preserved. B6-hFOLH1 mice can be used for research into the pathogenesis of hyperhomocysteinemia and various solid tumors like prostate cancer, as well as for the screening, development, and safety evaluation of FOLH1-targeted drugs.
Reference
Bakht MK, Beltran H. Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer. Nat Rev Urol. 2025 Jan;22(1):26-45.
Uijen MJM, Derks YHW, Merkx RIJ, Schilham MGM, Roosen J, Privé BM, van Lith SAM, van Herpen CML, Gotthardt M, Heskamp S, van Gemert WAM, Nagarajah J. PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports. Eur J Nucl Med Mol Imaging. 2021 Dec;48(13):4350-4368.
Devlin AM, Ling EH, Peerson JM, Fernando S, Clarke R, Smith AD, Halsted CH. Glutamate carboxypeptidase II: a polymorphism associated with lower levels of serum folate and hyperhomocysteinemia. Hum Mol Genet. 2000 Nov 22;9(19):2837-44.
Strain Strategy
The region from aa.45 to partial intron 2 of mouse Folh1 will be replaced with the human FOLH1 cDNA of the extracellular domain-3’UTR of mouse Folh1-WPRE-BGH pA cassette. The murine cytoplasmic-transmembrane domain will be preserved.
Figure 1. Gene editing strategy of B6-hFOLH1 Mice.
Application Area
FOLH1-targeted drug screening, development, and evaluation;
Research on the pathological mechanisms and therapeutic approaches of hyperhomocysteinemia;
Research on the pathological mechanisms and therapeutic approaches of various solid tumors like prostate cancer.
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