C57BL/6JCya-Lpar1em1flox/Cya
Common Name:
Lpar1-flox
Product ID:
S-CKO-02715
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Lpar1-flox
Strain ID
CKOCMP-14745-Lpar1-B6J-VA
Gene Name
Product ID
S-CKO-02715
Gene Alias
Edg2; Gpcr26; Kdt2; lpA1; vzg-1
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
4
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Lpar1em1flox/Cya mice (Catalog S-CKO-02715) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000055018
NCBI RefSeq
NM_172989
Target Region
Exon 3
Size of Effective Region
~2.1 kb
Detailed Document
Overview of Gene Research
Lpar1, also known as endothelial differentiation gene-2 receptor (Edg2), encodes a protein that can couple to G protein-coupled receptors (GPCRs). It participates in regulating cell proliferation, migration, survival, and apoptosis, and is found in almost all human tissues, being most abundant in the brain [2]. The LPA-LPAR1 signaling pathway is involved in multiple biological processes and diseases.
In the central nervous system (CNS), Lpar1 deletion causes neurodevelopmental disorders and CNS diseases such as brain cancer, neuropsychiatric disorders, demyelination diseases, and neuropathic pain [2]. In conditional Lpar1 null mutant mice, cre-mediated Lpar1 deletion using neural gene promoters for nestin, synapsin, or P0, as well as CD11b promoter, reduced PSNL-initiated pain responses, suggesting the involvement of Schwann cells, central and/or peripheral neurons, and microglia in mediating pain [5].
In the enteric nervous system, LPAR1 is enriched in enteric glia in mice and humans. Blocking LPAR1 in vivo with AM966 attenuated gastrointestinal motility in mice and produced marked enteric neuro-and gliopathy, and samples from humans with chronic intestinal pseudo-obstruction showed reduced glial LPAR1 expression [4].
In neuroblastoma, reduced LPAR1 expression promoted tumor cell migration, and the LPA-LPAR1 axis has tumor-suppressing effects [3].
In liver fibrosis, LPAR1 was identified as a therapeutic target on collagen-producing central vein-associated hepatic stellate cells, and blockade of LPAR1 inhibited liver fibrosis in a rodent NASH model [6].
In prostate cancer, LPAR1 was significantly downregulated, and high LPAR1 expression was correlated with favorable overall survival, and it was involved in immune cell activation, proliferation, differentiation, and migration [7].
In pulmonary fibrosis, LPA-mediated activation of LPAR1 contributes to the pathophysiology, and LPAR1 has gained interest as a pharmaceutical target [1,8].
In skin, lysophosphatidic acid induces keratinocyte differentiation and promotes skin barrier function through the LPAR1/LPAR5-RHO-ROCK-SRF axis [9].
In conclusion, Lpar1 plays crucial roles in multiple biological processes and diseases, including those related to the nervous system, cancer, fibrosis, and skin function. The use of gene knockout and conditional knockout mouse models has significantly contributed to understanding its role in these specific disease areas, providing insights into potential therapeutic targets.
References:
1. Luo, Ya-Li, Li, Yan, Zhou, Wen, Wang, Si-Yu, Liu, Yong-Qi. 2023. Inhibition of LPA-LPAR1 and VEGF-VEGFR2 Signaling in IPF Treatment. In Drug design, development and therapy, 17, 2679-2690. doi:10.2147/DDDT.S415453. https://pubmed.ncbi.nlm.nih.gov/37680863/
2. Xiao, Dongqiong, Su, Xiaojuan, Gao, Hu, Li, Xihong, Qu, Yi. 2021. The Roles of Lpar1 in Central Nervous System Disorders and Diseases. In Frontiers in neuroscience, 15, 710473. doi:10.3389/fnins.2021.710473. https://pubmed.ncbi.nlm.nih.gov/34385905/
3. Liu, Xiangjun, Pei, Mengmiao, Yu, Yongbo, Wang, Xiaolin, Gui, Jingang. 2022. Reduction of LPAR1 Expression in Neuroblastoma Promotes Tumor Cell Migration. In Cancers, 14, . doi:10.3390/cancers14143346. https://pubmed.ncbi.nlm.nih.gov/35884407/
4. Ahmadzai, Mohammad M, McClain, Jonathon L, Dharshika, Christine, De Giorgio, Roberto, Gulbransen, Brian D. . LPAR1 regulates enteric nervous system function through glial signaling and contributes to chronic intestinal pseudo-obstruction. In The Journal of clinical investigation, 132, . doi:10.1172/JCI149464. https://pubmed.ncbi.nlm.nih.gov/35166239/
5. Rivera, Richard R, Lin, Mu-En, Bornhop, Emily C, Chun, Jerold. 2020. Conditional Lpar1 gene targeting identifies cell types mediating neuropathic pain. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34, 8833-8842. doi:10.1096/fj.202000317R. https://pubmed.ncbi.nlm.nih.gov/32929779/
6. Dobie, Ross, Wilson-Kanamori, John R, Henderson, Beth E P, Marioni, John C, Henderson, Neil C. . Single-Cell Transcriptomics Uncovers Zonation of Function in the Mesenchyme during Liver Fibrosis. In Cell reports, 29, 1832-1847.e8. doi:10.1016/j.celrep.2019.10.024. https://pubmed.ncbi.nlm.nih.gov/31722201/
7. Shi, Jingqi, Jiang, Dongbo, Yang, Shuya, Lu, Yuchen, Yang, Kun. 2020. LPAR1, Correlated With Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer. In Frontiers in oncology, 10, 846. doi:10.3389/fonc.2020.00846. https://pubmed.ncbi.nlm.nih.gov/32656075/
8. Volkmann, Elizabeth R, Denton, Christopher P, Kolb, Martin, Allanore, Yannick, Khanna, Dinesh. 2024. Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis. In European respiratory review : an official journal of the European Respiratory Society, 33, . doi:10.1183/16000617.0015-2024. https://pubmed.ncbi.nlm.nih.gov/39009409/
9. Sumitomo, Akiko, Siriwach, Ratklao, Thumkeo, Dean, Aoki, Junken, Narumiya, Shuh. 2018. LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis. In The Journal of investigative dermatology, 139, 1010-1022. doi:10.1016/j.jid.2018.10.034. https://pubmed.ncbi.nlm.nih.gov/30447238/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen