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Successful lactation in Plgrkt-deficient female mice caused by a 1-bp deletion of exon4

Published online by Cambridge University Press:  06 April 2022

Takayuki Iwaki*
Affiliation:
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Yuki Tomonari
Affiliation:
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
Kazuo Umemura
Affiliation:
Department of Pharmacology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
*
Author for correspondence: Takayuki Iwaki, Email: tiwaki@hama-med.ac.jp

Abstract

Plasminogen (Pg) activation on the cell surface is important for various (patho)physiologic conditions, and Plg-RKT is a cell membrane protein that binds to Pg and promotes its activation. To evaluate the role of Plg-RKT in atherosclerosis, Plgrkt gene in Ldlr−/−/Apobec1−/− was modified using in vivo CRISPR/Cas9. Synthetic RNA for Plgrkt and Cas9 complex was electroporated into the fertilized eggs in the oviducts. Plgrkt deficient mice were established through a 1-bp deletion, and in this research communication we report their lactational ability. In contrast to Plgrkt−/− mice developed by a conventional method, these newly developed mice did not suffer lactation failure and could maintain their pups until weaning. The major obvious difference between these lines is the area of gene modification. The conventionally developed mouse possesses about 10 kb deletion of Plgrkt, which might relate to the lactation failure. Lactation failure is a lethal phenotype in mammals, and analyses of causative genes are especially important for dairy industries. Further genome-wide analyses with both Plgrkt−/− mice may help to establish causative genes for lactation failure.

Type
Research Article
Copyright
Copyright © The Author(s), 2022. Published by Cambridge University Press on behalf of Hannah Dairy Research Foundation

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References

Bhattacharya, S, Ploplis, VA and Castellino, FJ (2012) Bacterial plasminogen receptors utilize host plasminogen system for effective invasion and dissemination. Journal of Biomedicine and Biotechnology 2012, 482096.CrossRefGoogle ScholarPubMed
Castellino, FJ and McCance, SG (1997) The kringle domains of human plasminogen. Ciba Foundation Symposia 212, 4660, discussion 60–45.Google ScholarPubMed
Green, KA, Nielsen, BS, Castellino, FJ, Romer, J and Lund, LR (2006) Lack of plasminogen leads to milk stasis and premature mammary gland involution during lactation. Developmental Biology 299, 164175.CrossRefGoogle ScholarPubMed
Iwaki, T, Sandoval-Cooper, MJ, Brechmann, M, Ploplis, VA and Castellino, FJ (2006) A fibrinogen deficiency accelerates the initiation of LDL cholesterol-driven atherosclerosis via thrombin generation and platelet activation in genetically predisposed mice. Blood 107, 38833891.CrossRefGoogle ScholarPubMed
Lund, LR, Bjorn, SF, Sternlicht, MD, Nielsen, BS, Solberg, H, Usher, PA, Osterby, R, Christensen, IJ, Stephens, RW, Bugge, TH, Dano, K and Werb, Z (2000) Lactational competence and involution of the mouse mammary gland require plasminogen. Development (Cambridge, England) 127, 44814492.CrossRefGoogle ScholarPubMed
Mayer, M (1990) Biochemical and biological aspects of the plasminogen activation system. Clinical Biochemistry 23, 197211.CrossRefGoogle ScholarPubMed
Miles, LA, Hawley, SB, Baik, N, Andronicos, NM, Castellino, FJ and Parmer, RJ (2005) Plasminogen receptors: the sine qua non of cell surface plasminogen activation. Frontiers in Biosciences 10, 17541762.Google ScholarPubMed
Miles, LA, Baik, N, Lighvani, S, Khaldoyanidi, S, Varki, NM, Bai, H, Mueller, BM and Parmer, RJ (2017) Deficiency of plasminogen receptor, Plg-RKT, causes defects in plasminogen binding and inflammatory macrophage recruitment in vivo. Journal of Thrombosis and Haemostasis 15, 155162.CrossRefGoogle Scholar
Miles, LA, Baik, N, Bai, H, Makarenkova, HP, Kiosses, WB, Krajewski, S, Castellino, FJ, Valenzuela, A, Varki, NM, Mueller, BM and Parmer, RJ (2018) The plasminogen receptor, Plg-RKT, is essential for mammary lobuloalveolar development and lactation. Journal of Thrombosis and Haemostasis 16, 919932.CrossRefGoogle Scholar
Miyajima, C, Iwaki, T, Umemura, K, Ploplis, VA and Castellino, FJ (2018) Characterization of atherosclerosis formation in a murine model of type IIa human familial hypercholesterolemia. Biomedical Research International 2018, 1878964.CrossRefGoogle Scholar
Ny, L, Parmer, RJ, Shen, Y, Holmberg, S, Baik, N, Bäckman, A, Broden, J, Wilczynska, M, Ny, T and Miles, LA (2020) The plasminogen receptor, Plg-R(KT), plays a role in inflammation and fibrinolysis during cutaneous wound healing in mice. Cell Death and Disease 11, 1054.CrossRefGoogle Scholar
Ohtsuka, M, Sato, M, Miura, H, Takabayashi, S, Matsuyama, M, Koyano, T, Arifin, N, Nakamura, S, Wada, K and Gurumurthy, CB (2018) i-GONAD: a robust method for in situ germline genome engineering using CRISPR nucleases. Genome Biology 19, 25.CrossRefGoogle ScholarPubMed
Ploplis, VA, Carmeliet, P, Vazirzadeh, S, Van Vlaenderen, I, Moons, L, Plow, EF and Collen, D (1995) Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 92, 25852593.CrossRefGoogle ScholarPubMed
Samad, F, Bai, H, Baik, N, Haider, P, Zhang, Y, Rega-Kaun, G, Kaun, C, Prager, M, Wojta, J, Bui, Q, Chakrabarty, S, Wang, J, Parmer, RJ and Miles, LA (2021) The plasminogen receptor Plg-R(KT) regulates adipose function and metabolic homeostasis. Journal of Thrombosis and Haemostasis 20, 742-754.Google ScholarPubMed
Urano, T, Castellino, FJ and Suzuki, Y (2018) Regulation of plasminogen activation on cell surfaces and fibrin. Journal of Thrombosis and Haemostasis 16, 14871497.CrossRefGoogle ScholarPubMed
Whyte, CS, Morrow, GB, Baik, N, Booth, NA, Jalal, MM, Parmer, RJ, Miles, LA and Mutch, NJ (2021) Exposure of plasminogen and a novel plasminogen receptor, Plg-RKT, on activated human and murine platelets. Blood 137, 248257.CrossRefGoogle Scholar
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