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Group 3 Mast cell deficient mice models

Group 3 Mast cell deficient mice models. COST action BM1007 Training school Jerusalem January 2014. MZ. MZ. MZ. The Kit-deficient mouse models for mast cell research. WBB6F 1 - Kit W / Kit W -v. no mast cells no melanocytes lack in γδ T cells anemic neutropenia sterile.

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Group 3 Mast cell deficient mice models

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  1. Group 3 Mast cell deficient mice models COST action BM1007 Training school Jerusalem January 2014

  2. MZ MZ MZ • The Kit-deficient mouse models for mast cell research WBB6F1-KitW/KitW-v • nomastcells • nomelanocytes • lack in γδ T cells • anemic • neutropenia • sterile MC reaction Kit+/+ yes yes KitW/KitW-v no no yes ? yes, but deficient MZ

  3. MZ MZ MZ • The Kit-deficient mouse models for mast cell research C57B6-Kitsh/Kitsh(sash) MC reaction • nomastcells • nomelanocytes • neutrophilia • splenomegaly Kit+/+ yes yes no no Kitsh/Kitsh yes ? yes, but deficient MZ

  4. Available Kit-independent MC-deficient mouse models

  5. Selective ablation of mast cells or basophilsreduces peanut-induced anaphylaxis in mice ‏Reber, L. L., et al. Clinical and Translational Allergy(2013)‏

  6. Mast cell deficient mice models Mcpt5-Cre+;iDTR+ KitW-sh/W-sh neutrophil depleted-KitW-sh/W-sh

  7. Basophil deficient mice models Mcpt8DTR/+ • Ba10336 antibody

  8. Mast cell and basophil deficient mice models Cpa3-Cre;Mcl-1fl/fl

  9. Cre-Mediated Cell Ablation Contests Mast Cell Contribution in Models of Antibody andT Cell-Mediated Autoimmunity ‏ Feyerabend, Thorsten B., et al. Immunity (2011)‏ ‏

  10. Nippostrongylusbrasiliensis

  11. Antibody-Induced Arthritis Encephalomyelitis

  12. Mast Cells Are Key Promoters of Contact Allergy that Mediate the Adjuvant Effects of Haptens Dudeck, Anne, et al. Immunity 34.6 (2011)

  13. KitW-sh/W-shneutrophil depleted KitW/Wv KitW-sh/W-sh Mcpt5-Cre+;iDTR+ Mcpt5-Cre+R-DTA+

  14. Summary Kit dependent mutants Kit independent mutants • KitW/W-v • KitW-sh/W-sh • Mcpt5-Cre;R-DTA/iDTR • “Cre-Master”Cpa3Cre/+

  15. Conclusions No model is perfect ! Kit dependent mutants Kit independent mutants • Non specific immune effects • Compensation effect • Possible effects on other cells • Effects of apoptosis • Breeding / economical • Compensation effect Variable results depending on different animal strains/models, protocols, disease model etc.

  16. “ Based on the results obtained so far with both the older and newer models for MC research, we think that the most robust conclusions about what MCs can do (or don’t do) in various biological responses in vivo, and regarding the importance of such MC contributions, are likely to be derived from investigations that employ multiple informative model systems. This approach increases the cost of such work, but permits one to exploit the attractive features of the various models while keeping in mind the known and potential limitations in each of them. “ Reber, Marichal and Galli, 2012

  17. But still… Results obtained so far – Valuable information Availability / cost effective Take home message: always ask the right question!

  18. Suggestions for improvements:

  19. Thanks ! Thanks Frank! Questions ?

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