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Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.

Publication ,  Journal Article
Csepregi, JZ; Orosz, A; Zajta, E; Kása, O; Németh, T; Simon, E; Fodor, S; Csonka, K; Barátki, BL; Kövesdi, D; He, Y-W; Gácser, A; Mócsai, A
Published in: J Immunol
December 15, 2018

Mouse strains with specific deficiency of given hematopoietic lineages provide invaluable tools for understanding blood cell function in health and disease. Whereas neutrophils are dominant leukocytes in humans and mice, there are no widely useful genetic models of neutrophil deficiency in mice. In this study, we show that myeloid-specific deletion of the Mcl-1 antiapoptotic protein in Lyz2 Cre/Cre Mcl1 flox/flox (Mcl1 ΔMyelo) mice leads to dramatic reduction of circulating and tissue neutrophil counts without affecting circulating lymphocyte, monocyte, or eosinophil numbers. Surprisingly, Mcl1 ΔMyelo mice appeared normally, and their survival was mostly normal both under specific pathogen-free and conventional housing conditions. Mcl1 ΔMyelo mice were also able to breed in homozygous form, making them highly useful for in vivo experimental studies. The functional relevance of neutropenia was confirmed by the complete protection of Mcl1 ΔMyelo mice from arthritis development in the K/B×N serum-transfer model and from skin inflammation in an autoantibody-induced mouse model of epidermolysis bullosa acquisita. Mcl1 ΔMyelo mice were also highly susceptible to systemic Staphylococcus aureus or Candida albicans infection, due to defective clearance of the invading pathogens. Although neutrophil-specific deletion of Mcl-1 in MRP8-CreMcl1 flox/flox (Mcl1 ΔPMN) mice also led to severe neutropenia, those mice showed an overt wasting phenotype and strongly reduced survival and breeding, limiting their use as an experimental model of neutrophil deficiency. Taken together, our results with the Mcl1 ΔMyelo mice indicate that severe neutropenia does not abrogate the viability and fertility of mice, and they provide a useful genetic mouse model for the analysis of the role of neutrophils in health and disease.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2018

Volume

201

Issue

12

Start / End Page

3793 / 3803

Location

United States

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Neutrophils
  • Neutropenia
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
 

Citation

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Csepregi, J. Z., Orosz, A., Zajta, E., Kása, O., Németh, T., Simon, E., … Mócsai, A. (2018). Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form. J Immunol, 201(12), 3793–3803. https://doi.org/10.4049/jimmunol.1701803
Csepregi, Janka Zsófia, Anita Orosz, Erik Zajta, Orsolya Kása, Tamás Németh, Edina Simon, Szabina Fodor, et al. “Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.J Immunol 201, no. 12 (December 15, 2018): 3793–3803. https://doi.org/10.4049/jimmunol.1701803.
Csepregi JZ, Orosz A, Zajta E, Kása O, Németh T, Simon E, et al. Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form. J Immunol. 2018 Dec 15;201(12):3793–803.
Csepregi, Janka Zsófia, et al. “Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form.J Immunol, vol. 201, no. 12, Dec. 2018, pp. 3793–803. Pubmed, doi:10.4049/jimmunol.1701803.
Csepregi JZ, Orosz A, Zajta E, Kása O, Németh T, Simon E, Fodor S, Csonka K, Barátki BL, Kövesdi D, He Y-W, Gácser A, Mócsai A. Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form. J Immunol. 2018 Dec 15;201(12):3793–3803.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2018

Volume

201

Issue

12

Start / End Page

3793 / 3803

Location

United States

Related Subject Headings

  • Staphylococcus aureus
  • Staphylococcal Infections
  • Neutrophils
  • Neutropenia
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans