Mouse Proprotein Convertase 9/PCSK9 Quantikine ELISA Kit

• Reactivity: Mu
• Applications: ELISA
• Conjugate: HRP

Mouse Proprotein Convertase 9/PCSK9 Quantikine ELISA Kit Summary

• Background: The Quantikine Mouse PCSK9 Immunoassay is a 4.5 hour solid-phase ELISA designed to measure mouse PCSK9 in cell culture supernates, cell lysates, serum, and plasma. It contains NS0-expressed recombinant mouse PCSK9 and antibodies raised against the recombinant factor. This immunoassay has been shown to accurately quantitate the recombinant factor. Results obtained using natural mouse PCSK9 sh...owed linear curves that were parallel to the standard curves obtained using the Quantikine kit standards. These results indicate that this kit can be used to determine relative mass values for naturally occurring mouse PCSK9.
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• Specificity: Natural and recombinant mouse PCSK9. This kit detects 60 kDa, 53 kDa, and LDLR-complexed recombinant mouse PCSK9.
• Source: N/A
• Assay Type: Solid Phase Sandwich ELISA
• Inter-Assay: See PDF Datasheet for details
• Intra-Assay: See PDF Datasheet for details
• Spike Recovery: See PDF Datasheet for details
• Sample Volume: See PDF Datasheet for details
• Gene: Pcsk9

Applications/Dilutions

• Dilutions:
  • ELISA
• Application Notes: No significant interference observed with available related molecules.

Packaging, Storage & Formulations

• Storage: Store the unopened product at 2 - 8 °C. Do not use past expiration date.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Mouse Proprotein Convertase 9/PCSK9 Quantikine ELISA Kit

• EC 3.4.21
• EC 3.4.21.111
• FH3
• FH3neural apoptosis regulated convertase 1
• FHCL3
• HCHOLA3
• hypercholesterolemia, autosomal dominant 3
• LDLCQ1
• NARC1
• NARC-1
• NARC-1convertase subtilisin/kexin type 9 preproprotein
• NARC1EC 3.4.21.-
• Neural apoptosis-regulated convertase 1
• PC9
• PCSK9
• Proprotein Convertase 9
• proprotein convertase subtilisin/kexin type 9
• Subtilisin/kexin-like protease PC9

Background

PCSK9 (proprotein convertase subtilisin kexin 9), also called proprotein convertase 9 or NARC-1 (neural apoptosis-regulated convertase 1), is a member of the proteinase K subfamily of subtilisinrelated serine endoproteases. Mouse PCSK9 cDNA encodes 694 amino acids, including a signal peptide, a prodomain, and a catalytic domain. PCSK9 is highly expressed in the liver, intestine, and kidney. It is initially synthesized as a soluble 74 kDa precursor protein. In the endoplasmic reticulum, it undergoes autocatalytic intramolecular cleavage to generate a 14 kDa prodomain and a 60 kDa catalytic domain. While within the secretion pathway, the prodomain remains associated and functions as a chaperone for the catalytic domain (1-4). During secretion, a portion of active PCSK9 may undergo additional N-terminal proteolysis by furin or proprotein convertase 5/6A, creating an inactive 53 kDa form (5). This cleavage site is conserved between mouse and human or rat PCSK9, which share 78% or 93% amino acid sequence identity, respectively. While the 60 kDa protein is the major form, its ratio with the 53 kDa forms is variable in humans (5, 6). 

The primary physiologic function of PCSK9 is to mediate the degradation of low density lipoprotein receptor (LDLR). Early observations indicated that gain-of-function missense mutations in the human PCSK9 gene can cause an autosomal dominant form of hypercholesterolemia (7, 8). The expression of PCSK9 is also upregulated by the sterol regulatory element binding proteins (SREBPs), a family of transcription factors that are responsible for the upregulation of genes involved in cholesterol and fatty acid metabolism, such as the LDLR gene (9, 10). Further experimental evidence revealed that when the mouse PCSK9 gene is deleted, LDLR expression in hepatocytes is increased. Conversely, PCSK9 over-expression decreases liver LDLR protein expression (11, 12). In humans, genetic analyses have shown that individuals who have nonsense or loss-of-function mutations in the PCSK9 gene have significantly lower plasma LDL cholesterol levels, while in mouse, administration of a PCSK9 neutralizing antibody or antisense oligonucleotides lowers serum cholesterol (1, 13-15). These investigations clearly indicate that PCSK9 plays a key role in reducing the hepatic LDLR levels. Paradoxically, administration of cholesterol-lowering drugs such as statins appear to enhance production of PCSK9 (6). 

The underlying mechanism of cholesterol regulation by PCSK9 is as follows: under normal physiologic conditions, the LDLR is internalized at the cell surface and directed to the endosomes in order to be recycled back to the cell surface. PCSK9 binds to the EGF domain of the LDLR and prevents LDLR from being sorted to the endosomes. Instead, the PCSK9/LDLR complex is redistributed to the lysosomes for degradation (16-18). As such, PCSK9 regulates the amount of LDLR in the circulation and hence, modulates cholesterol levels. Serum PCSK9 concentrations have been found to be directly associated with cholesterol levels (19, 20). Since PCSK9 loss-of-function mutations strikingly reduce risk of coronary heart diseases, PCSK9 has become an attractive drug target (1, 21, 22). One approach is to generate small molecules that are able to interfere with PCSK9 autoactivation and its interaction with LDLR. Other approaches aiming to reduce the amount of PCSK9 in the circulation, such as small interfering RNAs (siRNAs), have also shown promise (23, 24).

⚠ WARNING: This product can expose you to chemicals including N,N-Dimethylforamide, which is known to the State of California to cause cancer. For more information, go to www.P65Warnings.ca.gov.

Publications for Proprotein Convertase 9/PCSK9 (MPC900)(30)

Publications using MPC900

• Cappelluti, MA;Mollica Poeta, V;Valsoni, S;Quarato, P;Merlin, S;Merelli, I;Lombardo, A; Durable and efficient gene silencing in vivo by hit-and-run epigenome editing Nature 2024-02-28 [PMID: 38418872] (Mouse)
• Franko, N;da Silva Santinha, AJ;Xue, S;Zhao, H;Charpin-El Hamri, G;Platt, RJ;Teixeira, AP;Fussenegger, M; Integrated compact regulators of protein activity enable control of signaling pathways and genome-editing in vivo Cell discovery 2024-01-23 [PMID: 38263404] (Mouse)
• Han, W;Gao, BQ;Zhu, J;He, Z;Li, J;Yang, L;Chen, J; Design and application of the transformer base editor in mammalian cells and mice Nature protocols 2023-10-04 [PMID: 37794072] (Transgenic Mouse)
• Schmidheini, L;Mathis, N;Marquart, KF;Rothgangl, T;Kissling, L;Böck, D;Chanez, C;Wang, JP;Jinek, M;Schwank, G; Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility Nature chemical biology 2023-09-21 [PMID: 37735239] (Mouse)
• Bestas, B;Wimberger, S;Degtev, D;Madsen, A;Rottner, AK;Karlsson, F;Naumenko, S;Callahan, M;Touza, JL;Francescatto, M;Möller, CI;Badertscher, L;Li, S;Cerboni, S;Selfjord, N;Ericson, E;Gordon, E;Firth, M;Chylinski, K;Taheri-Ghahfarokhi, A;Bohlooly-Y, M;Snowden, M;Pangalos, M;Nuttall, B;Akcakaya, P;Sienski, G;Maresca, M; A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo Nature communications 2023-09-06 [PMID: 37673883] (Mouse)
• L Goksøyr, M Skrzypczak, M Sampson, MA Nielsen, A Salanti, TG Theander, AT Remaley, WA De Jongh, AF Sander A cVLP-Based Vaccine Displaying Full-Length PCSK9 Elicits a Higher Reduction in Plasma PCSK9 Than Similar Peptide-Based cVLP Vaccines Vaccines, 2022-12-20;11(1):. 2022-12-20 [PMID: 36679847] (Mouse)
• D Pakalnišky, T Schönberge, B Strobel, B Stierstorf, T Lamla, M Schuler, M Lenter Rosa26-LSL-dCas9-VPR: a versatile mouse model for tissue specific and simultaneous activation of multiple genes for drug discovery Scientific Reports, 2022-11-10;12(1):19268. 2022-11-10 [PMID: 36357523] (Transgenic Mouse)
• CT Stomberski, NM Venetos, HL Zhou, Z Qian, BR Collison, SJ Field, RT Premont, JS Stamler A multienzyme S-nitrosylation cascade regulates cholesterol homeostasis Cell Reports, 2022-10-25;41(4):111538. 2022-10-25 [PMID: 36288700] (Mouse)
• PW Chen, SY Tseng, HY Chang, CH Lee, TH Chao Diverse Effects of Cilostazol on Proprotein Convertase Subtilisin/Kexin Type 9 between Obesity and Non-Obesity International Journal of Molecular Sciences, 2022-08-29;23(17):. 2022-08-29 [PMID: 36077166] (Mouse)
• Tong, H;Huang, J;Xiao, Q;He, B;Dong, X;Liu, Y;Yang, X;Han, D;Wang, Z;Wang, X;Ying, W;Zhang, R;Wei, Y;Xu, C;Zhou, Y;Li, Y;Cai, M;Wang, Q;Xue, M;Li, G;Fang, K;Zhang, H;Yang, H; High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects Nature biotechnology 2023-01-01 [PMID: 35953673] (Mouse)
• PF Lebeau, JH Byun, K Platko, P Saliba, M Sguazzin, ME MacDonald, G Paré, GR Steinberg, LJ Janssen, SA Igdoura, MA Tarnopolsk, SR Wayne Chen, NG Seidah, J Magolan, RC Austin Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance Nature Communications, 2022-02-09;13(1):770. 2022-02-09 [PMID: 35140212] (Mouse)
• R Deshycka, V Sudaryo, NJ Huang, Y Xie, LY Smeding, MK Choi, HL Ploegh, HF Lodish, N Pishesha Engineered red blood cells carrying PCSK9 inhibitors persistently lower LDL and prevent obesity PLoS ONE, 2021-11-03;16(11):e0259353. 2021-11-03 [PMID: 34731223] (Mouse)
• T Rothgangl, MK Dennis, PJC Lin, R Oka, D Witzigmann, L Villiger, W Qi, M Hruzova, L Kissling, D Lenggenhag, C Borrelli, S Egli, N Frey, N Bakker, JA Walker, AP Kadina, DV Victorov, M Pacesa, S Kreutzer, Z Kontarakis, A Moor, M Jinek, D Weissman, M Stoffel, R van Boxtel, K Holden, N Pardi, B Thöny, J Häberle, YK Tam, SC Semple, G Schwank In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels Nature Biotechnology, 2021-05-19;0(0):. 2021-05-19 [PMID: 34012094] (Mouse)
• L Wang, W Xue, H Zhang, R Gao, H Qiu, J Wei, L Zhou, YN Lei, X Wu, X Li, C Liu, J Wu, Q Chen, H Ma, X Huang, C Cai, Y Zhang, B Yang, H Yin, L Yang, J Chen Eliminating base-editor-induced genome-wide and transcriptome-wide off-target mutations Nature Cell Biology, 2021-05-10;23(5):552-563. 2021-05-10 [PMID: 33972728] (Mouse)
• B Ibold, J Tiemann, I Faust, U Ceglarek, J Dittrich, TGMF Gorgels, AAB Bergen, O Vanakker, M Van Gils, C Knabbe, D Hendig Genetic deletion of Abcc6 disturbs cholesterol homeostasis in mice Scientific Reports, 2021-01-22;11(1):2137. 2021-01-22 [PMID: 33483533] (Mouse)
• JR Backstrom, J Sheng, MC Wang, A Bernardo-C, TS Rex Optimization of S.�aureus dCas9 and CRISPRi Elements for a Single Adeno-Associated Virus that Targets an Endogenous Gene Mol Ther Methods Clin Dev, 2020-09-06;19(0):139-148. 2020-09-06 [PMID: 33024795] (Mouse)
• F Moghadam, R LeGraw, JJ Velazquez, NC Yeo, C Xu, J Park, A Chavez, MR Ebrahimkha, S Kiani Synthetic immunomodulation with a CRISPR super-repressor in vivo Nat. Cell Biol., 2020-09-03;22(9):1143-1154. 2020-09-03 [PMID: 32884147] (Mouse)
• A Carreras, LS Pane, R Nitsch, K Madeyski-B, M Porritt, P Akcakaya, A Taheri-Gha, E Ericson, M Bjursell, M Perez-Alca, F Seeliger, M Althage, R Knöll, R Hicks, LM Mayr, R Perkins, D Lindén, J Borén, M Bohlooly-Y, M Maresca In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model BMC Biol., 2019-01-15;17(1):4. 2019-01-15 [PMID: 30646909] (Mouse)
• AC Rossidis, JD Stratigis, AC Chadwick, HA Hartman, NJ Ahn, H Li, K Singh, BE Coons, L Li, W Lv, PW Zoltick, D Alapati, W Zacharias, R Jain, EE Morrisey, K Musunuru, WH Peranteau In utero CRISPR-mediated therapeutic editing of metabolic genes Nat. Med., 2018-10-08;24(10):1513-1518. 2018-10-08 [PMID: 30297903] (Mouse)
• P Akcakaya, ML Bobbin, JA Guo, J Malagon-Lo, K Clement, SP Garcia, MD Fellows, MJ Porritt, MA Firth, A Carreras, T Baccega, F Seeliger, M Bjursell, SQ Tsai, NT Nguyen, R Nitsch, LM Mayr, L Pinello, M Bohlooly-Y, MJ Aryee, M Maresca, JK Joung In vivo CRISPR editing with no detectable genome-wide off-target mutations Nature, 2018-09-12;0(0):. 2018-09-12 [PMID: 30209390] (Mouse)
• PI Thakore, JB Kwon, CE Nelson, DC Rouse, MP Gemberling, ML Oliver, CA Gersbach RNA-guided transcriptional silencing in vivo with S. aureus CRISPR-Cas9 repressors Nat Commun, 2018-04-26;9(1):1674. 2018-04-26 [PMID: 29700298] (Mouse)
• AC Chadwick, NH Evitt, W Lv, K Musunuru Reduced Blood Lipid Levels With In Vivo CRISPR-Cas9 Base Editing of ANGPTL3 Circulation, 2018-02-27;137(9):975-977. 2018-02-27 [PMID: 29483174] (Mouse)
• Y Masuda, S Yamaguchi, C Suzuki, T Aburatani, Y Nagano, R Miyauchi, E Suzuki, N Yamamura, K Nagatomo, H Ishihara, K Okuno, F Nara, G Matschiner, R Hashimoto, T Takahashi, T Nishizawa Generation and Characterization of a Novel Small Biologic Alternative to Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Antibodies, DS-9001a, Albumin Binding Domain-Fused Anticalin Protein J. Pharmacol. Exp. Ther., 2018-02-20;365(2):368-378. 2018-02-20 [PMID: 29463608] (Mouse)
• R Kawakami, Y Nozato, H Nakagami, Y Ikeda, M Shimamura, S Yoshida, J Sun, T Kawano, Y Takami, T Noma, H Rakugi, T Minamino, R Morishita Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice PLoS ONE, 2018-02-13;13(2):e0191895. 2018-02-13 [PMID: 29438441] (Mouse)
• M Rogers, N Maldonado-, JD Hutcheson, C Goettsch, S Goto, I Yamada, T Faits, H Sesaki, M Aikawa, E Aikawa Dynamin-Related Protein 1 Inhibition Attenuates Cardiovascular Calcification in the Presence of Oxidative Stress Circ. Res., 2017-06-12;0(0):. 2017-06-12 [PMID: 28607103] (Mouse)
• Bin Dong Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters J. Lipid Res, 2016-12-09;0(0):. 2016-12-09 [PMID: 27940481] (Hamster)
• Paul Lebeau Endoplasmic reticulum stress and Ca2+ depletion differentially modulate the sterol-regulatory protein PCSK9 to control lipid metabolism J. Biol. Chem, 2016-12-01;0(0):. 2016-12-01 [PMID: 27909053] (Mouse)
• Shende V, Wu M, Singh A, Dong B, Kan C, Liu J Reduction of circulating PCSK9 and LDL-C levels by liver-specific knockdown of HNF1alpha in normolipidemic mice. J Lipid Res, 2015-02-04;56(4):801-9. 2015-02-04 [PMID: 25652089] (Mouse)
• Dong B, Li H, Singh A, Cao A, Liu J Inhibition of PCSK9 transcription by berberine involves down-regulation of hepatic HNF1alpha protein expression through the ubiquitin-proteasome degradation pathway. J Biol Chem, 2014-12-24;290(7):4047-58. 2014-12-24 [PMID: 25540198] (Hamster, Mouse)
• Ding Q, Strong A, Patel K, Ng S, Gosis B, Regan S, Cowan C, Rader D, Musunuru K Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing. Circ Res, 2014-06-10;115(5):488-92. 2014-06-10 [PMID: 24916110] (Mouse)

Bioinformatics

• Gene Symbol: Pcsk9