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| Research Progress on Mastitis Related Genes Regulation and Genetic Modification Models |
| QIU Shuang1, GUO Zi-Rong1, CHEN Li-Qiang1, ZHU Yi-Jing2, BAI Hui3, ZHANG Li-Guo2,*, SU Xiao-Hu1,* |
1 Schoolof Life Sciences, Inner Mongolia University, Hohhot 010020, China;
2 Ulanqab Animal Husbandry Workstation of Inner Mongolia Autonomous Region, Ulanqab 012000, China;
3 Institute of Animal Husbandry, Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences, Hohhot 010031, China |
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Abstract Mastitis is one of the major threats that affects the production performance of dairy livestock. However, the traditional antibiotic application strategy would lead to drug residues and resistance. This review systematically summarized research progress on mastitis-regulating genes to explore novel prevention and treatment strategies, including inflammatory pathway genes (Toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB)), chemokine genes (interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α)), antimicrobial genes (lysozyme (LYZ), β-defensin-4 (DEFB4), lactoferrin (LF)), and apoptosis-autophagy genes such as B cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (BAX), autophagy-related gene 5 (ATG5), microRNA-223 (miR-223) and other apoptosis-autophagy genes. And this review summarized advances in genetic modification models for mastitis regulation, including mice (Mus musculus), dairy goats (Capra hircus), and dairy cows (Bos taurus). This review provides a technical reference for the novel breeding materials creation of mastitis-resistant dairy livestock and the theoretical guidance for the development of targeted prevention and control strategies for mastitis.
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Received: 08 September 2025
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Corresponding Authors:
*13947144670@139.com; 87939599@qq.com
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[1] 安冬, 王军, 刘红羽, 等. 2018. DNA甲基化参与LPS诱导的奶牛乳腺上皮细胞TNF-α表达[J]. 中国兽医杂志, 54: 30-32+36+123.
(An D, Wang J, Liu H Y, et al. 2018. DNA methylation participates in LPS-induced TNF-α expression in bovine mammary epithelial cells[J]. Chinese Journal of Veterinary Science, 54: 30-32+36+123.)
[2] 哈斯格日图. 2018. 牛乳中内源性乳铁蛋白在牛乳房炎治疗中的影响研究[D]. 硕士学位论文, 西北农林科技大学, 导师: 岳田利, pp.7-10.
(Hasgertu.2018. Study on the effect of endogenous lactoferrin in bovine milk mastitis treatment[D]. Thesis for M.S., Northwest A&F University, Supervisor: Yue T L, pp.7-10.)
[3] 纪晓霞, 刘小倩, 刘颖, 等. 2019.高精料日粮诱导奶牛乳腺应激和凋亡中血管紧张素转化酶2的作用[J]. 南京农业大学学报, 42: 513-518.
(Ji X X, Liu X Q, Liu Y, et al.2019. The role of angiotensin-converting enzyme 2 in inducing mammary gland stress and apoptosis in dairy cows fed a high-concentrate diet[J]. Journal of Nanjing Agricultural University, 42: 513-518.)
[4] 沈聪. 2019. 乳铁蛋白对LPS诱导的奶牛原代肝细胞炎症反应的抑制作用[D]. 硕士学位论文, 西北农林科技大学, 导师: 董强, pp. 3-8.
(Shen C.2019. Inhibitory effect of lactoferrin on LPS-induced inflammatory response in primary bovine hepatocytes[D]. Thesis for M.S., Northwest A&F University, Supervisor: Dong Q, pp. 3-8.)
[5] 孙雅君. 2021. 奶牛乳腺炎源金黄色葡萄球菌耐药性相关基因的检测与耐药菌株表型异质性分析[D]. 博士学位论文, 西北农林科技大学, 导师: 赵辛, pp.3-4.
(Sun Y J.2021. Detection of antimicrobial resistance-related genes in Staphylococcus aureus isolated from bovine mastitis and analysis of phenotypic heterogeneity in resistant strains[D]. Thesis for Ph.D., Northwest A&F University, Supervisor: Zhao X, pp. 3-4.)
[6] 闫晓斌, 高瑞雄, 袁凯, 等. 2024. 乳铁蛋白功能及作用效果[J]. 食品工业, 45: 223-229.
(Yan X B, Gao R X, Yuan K, et al.2024. Functions and effects of lactoferrin[J]. Food Industry, 45: 223-229.)
[7] 杨彩霞, 杨敏, 王根林, 等. 2022. TNF-α诱导小鼠乳腺上皮细胞凋亡和程序性坏死研究[J]. 南京农业大学学报, 45: 147-155.
(Yang C X, Yang M, Wang G L, et al.2022. TNF-α induces apoptosis and programmed necrosis in mouse mammary epithelial cells[J]. Journal of Nanjing Agricultural University, 45: 147-155.)
[8] Alan A, Alan E, Arslan K, et al.2022. LPS- and LTA-induced expression of TLR4, MyD88, and TNF-alpha in lymph nodes of the akkaraman and romanov lambs[J]. Microscopy and Microanalysis, 28(6): 2078-2092.
[9] Cao D, Luo J, Chen D, et al.2016. CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells[J]. Scientific Reports, 6: 23132.
[10] Chen H, Liu C, Xiang M, et al.2022. Contribution of the mutation rs8193069 in TLR4 to mastitis resistance and performance in Holstein cows in southern China[J]. Veterinary Medicine and Science, 8(1): 357-366.
[11] Du M, Xie X, Yang S, et al.2021. Lysozyme-like protein produced by Bifidobacterium longum regulates human gut microbiota using in vitro models[J]. Molecules, 26(21): 6480.
[12] Feng R, Zhao J, Zhang Q, et al.2024. Generation of anti-mastitis gene-edited dairy goats with enhancing lysozyme expression by inflammatory regulatory sequence using ISDra2-TnpB system[J]. Advanced Science, 11(38): e2404408.
[13] Gunther J, Esch K, Poschadel N, et al.2011. Comparative kinetics of Escherichia coli- and Staphylococcus aureus-specific activation of key immune pathways in mammary epithelial cells demonstrates that S. aureus elicits a delayed response dominated by interleukin-6 (IL-6) but not by IL-1A or tumor necrosis factor alpha[J]. Infection and Immunity, 79(2): 695-707.
[14] Harapas C R, Robinson K S, Lay K, et al.2022. DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1/IL-1 signaling[J]. Science Immunology, 7(75): eabi4611.
[15] Haroon M, Kang S C.2025. Kaempferol suppresses TLR-2 and TLR-4 coactivation by attenuation of LPS/LTA-induced inflammation and cellular stress[J]. Molecular Biology Reports, 52(1): 870.
[16] Jiang L, Li Q, Liao H, et al.2025. Enhancing agricultural productivity in dairy cow mastitis management: Innovations in non-antibiotic treatment technologies[J]. Veterinary Sciences, 12(7): 662.
[17] Johnzon C F, Dahlberg J, Gustafson A M, et al.2018. The effect of lipopolysaccharide-induced experimental bovine mastitis on clinical parameters, inflammatory markers, and the metabolome: A kinetic approach[J]. Frontiers in Immunology, 9: 1487.
[18] Li J, Liang Y, Su M, et al.2023. Characterization of a novel LTA/LPS-binding antimicrobial and anti-inflammatory temporin peptide from the skin of Fejervary limnocharis (Anura: Ranidae)[J]. Biochemical Pharmacology, 210: 115471.
[19] Liu J, Luo Y, Liu Q, et al.2013. Production of cloned embryos from caprine mammary epithelial cells expressing recombinant human beta-defensin-3[J]. Theriogenology, 79(4): 660-666.
[20] Liu X, Mi S, Dari G, et al.2025. Functional validation to explore the protective role of miR-223 in Staphylococcus aureus-induced bovine mastitis[J]. Journal of Animal Science and Biotechnology, 16(1): 34.
[21] Liu X, Wang Y, Tian Y, et al.2014. Generation of mastitis resistance in cows by targeting human lysozyme gene to beta-casein locus using zinc-finger nucleases[J]. Proceedings of the Royal Society B: Biological Sciences, 281(1780): 20133368.
[22] Liu Y, Zhang H, Dong S, et al.2022. Secretion of IFN-gamma by transgenic mammary epithelial cells in vitro reduced mastitis infection risk in goats[J]. Frontiers in Veterinary Science, 9: 898635.
[23] Moyes K M, Drackley J K, Morin D E, et al.2009. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPARgamma signaling as potential mechanism for the negative relationships between immune response and lipid metabolism[J]. BioMed Central Genomics, 10: 542.
[24] Neerukonda M, Pavuluri S, Sharma I, et al.2019. Functional evaluation of a monotreme-specific antimicrobial protein, EchAMP, against experimentally induced mastitis in transgenic mice[J]. Transgenic Research, 28(5-6): 573-587.
[25] Neumann S, Siegert S, Fischer A.2023. beta-defensin-4 as an endogenous biomarker in cows with mastitis[J]. Frontiers in Veterinary Science, 10: 1154386.
[26] Ruegg P L.2017. A 100-year review: Mastitis detection, management, and prevention[J]. Journal of Dairy Science, 100(12): 10381-10397.
[27] Saenz-de-Juano M D, Silvestrelli G, Bauersachs S, et al.2022. Determining extracellular vesicles properties and miRNA cargo variability in bovine milk from healthy cows and cows undergoing subclinical mastitis[J]. BioMed Central Genomics, 23(1): 189.
[28] Satheesan L, Dang A K, Alex R.2025. Cytokine interactions and chemokine dysregulations in mastitis immunopathogenesis: insights from transcriptomic profiling of milk somatic cells in tropical Sahiwal (Bos indicus) cows[J]. Frontiers in Immunology, 16: 1554341.
[29] Shandilya U K, Sharma A, Mallikarjunappa S, et al.2021. CRISPR-Cas9-mediated knockout of TLR4 modulates Mycobacterium avium ssp. paratuberculosis cell lysate-induced inflammation in bovine mammary epithelial cells[J]. Journal of Dairy Science, 104(10): 11135-11146.
[30] Sharma B S, Abo-Ismail M K, Schenkel F S, et al.2015. Association of TLR4 polymorphisms with Mycobacterium avium subspecies paratuberculosis infection status in Canadian Holsteins[J]. Animal Genetics, 46(5): 560-565.
[31] Sharma B S, Jansen G B, Karrow N A, et al.2006. Detection and characterization of amplified fragment length polymorphism markers for clinical mastitis in Canadian Holsteins[J]. Journal of Dairy Science, 89(9): 3653-3663.
[32] Sharun K, Dhama K, Tiwari R, et al.2021. Advances in therapeutic and managemental approaches of bovine mastitis: A comprehensive review[J]. Veterinary Quarterly, 41(1): 107-136.
[33] Shinozuka Y, Kawai K, Takeda A, et al.2019. Influence of oxytetracycline susceptibility as a first-line antibiotic on the clinical outcome in dairy cattle with acute Escherichia coli mastitis[J]. Journal of Veterinary Medical Science, 81(6): 863-868.
[34] Simojoki H, Hyvonen P, Orro T, et al.2010. High concentration of human lactoferrin in milk of rhLf-transgenic cows relieves signs of bovine experimental Staphylococcus chromogenes intramammary infection[J]. Veterinary Immunology and Immunopathology, 136(3-4): 265-271.
[35] Strandberg Y, Gray C, Vuocolo T, et al.2005. Lipopolysaccharide and lipoteichoic acid induce different innate immune responses in bovine mammary epithelial cells[J]. Cytokine, 31(1): 72-86.
[36] Szyda J, Mielczarek M, Fraszczak M, et al.2019. The genetic background of clinical mastitis in Holstein-Friesian cattle[J]. Animal, 13(10): 2156-2163.
[37] Wall R, Powell A, Sohn E, et al.2009. Enhanced host immune recognition of mastitis causing Escherchia coli in CD-14 transgenic mice[J]. Animal Biotechnology, 20(1): 1-14.
[38] Wang H, Wang X, Li X, et al.2019. A novel long non-coding RNA regulates the immune response in MAC-T cells and contributes to bovine mastitis[J]. Biochemistry, Genetics and Molecular Biology, 286(9): 1780-1795.
[39] Wang N, Ma Q, Peng P, et al.2020. Autophagy and ubiquitin-proteasome system coordinate to regulate the protein quality control of neurodegenerative disease-associated DCTN1[J]. Neurotoxicity Research, 37(1): 48-57.
[40] Yan Y, Zhu K, Fan M, et al.2023. Immunolocalization of antibacterial peptide S100A7 in mastitis goat mammary gland and lipopolysaccharide induces the expression and secretion of S100A7 in goat mammary gland epithelial cells via TLR4/NFkappaB signal pathway[J]. Animal Biotechnology, 34(7): 2701-2713.
[41] Yang W, Zerbe H, Petzl W, et al.2008. Bovine TLR2 and TLR4 properly transduce signals from Staphylococcus aureus and E. coli, but S. aureus fails to both activate NF-kappaB in mammary epithelial cells and to quickly induce TNFalpha and interleukin-8 (CXCL8) expression in the udder[J]. Molecula Immunology, 45(5): 1385-1397.
[42] Ying Y T, Yang J, Tan X, et al.2021. Escherichia coli and Staphylococcus aureus differentially regulate Nrf2 pathway in bovine mammary epithelial cells: Relation to distinct innate immune response[J]. Cells, 10(12): 3426.
[43] Zhao H, Wu L, Yan G, et al.2021. Inflammation and tumor progression: Signaling pathways and targeted intervention[J]. Signal Transduction and Targeted Therapy, 6(1): 263.
[44] Zhao W, Xu M, Barkema H W, et al.2022. Prototheca bovis induces autophagy in bovine mammary epithelial cells via the HIF-1alpha and AMPKalpha/ULK1 pathway[J]. Frontiers in Immunology, 13: 934819. |
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