Deletion of IKK2 in haematopoietic cells of adult mice leads to elevated interleukin-6, neutrophilia and fatal gastrointestinal inflammation
Karla C Fischer, Carmel P Daunt, Cedric S Tremblay, Sheila Dias, James E Vince, Anissa M Jabbour
CELL DEATH & DISEASE | SPRINGERNATURE | Published : 2021
The IκB kinase complex, consisting of IKK1, IKK2 and the regulatory subunit NEMO, is required for NF-κB signalling following the activation of several cell surface receptors, such as members of the Tumour Necrosis Factor Receptor superfamily and the Interleukin-1 Receptor. This is critical for haematopoietic cell proliferation, differentiation, survival and immune responses. To determine the role of IKK in the regulation of haematopoiesis, we used the Rosa26Cre-ERT2 Cre/lox recombination system to achieve targeted, haematopoietic cell-restricted deletion of the genes for IKK1 or IKK2 in vivo. We found that the IKK complex plays a critical role in haematopoietic cell development and function...View full abstract
Awarded by Australian National Health and Medical Research Council (NHMRC)
We thank the staff in the WEHI Bio service facility C. Stivala, N. Lynch and J. Mansheim and team, as well as the staff in the AMREP animal facility P. O'Hare, S. Jansen and team for expert animal care and help with experiments with mice; we thank J. Corbin for automated blood analysis (Avida); we thank S. Monard and his team from the WEHI flow cytometry facility as well as G. Paukovics and his team from the AMREP flow cytometry facility for their help with flow cytometry; we thank the staff in the WEHI histology department and the staff from the Monash histology platform in assisting in the preparation of samples for histological analysis. We thank M. Pasparakis for providing the IKK1<SUP>fl/fl</SUP> and IKK2<SUP>fl/fl</SUP> mice. We thank D.L. Vaux and A. Strasser for critical comments and advice and for their input and guidance in editing this paper. Funding statement: This work was supported by scholarships to KCF from The University of Melbourne (MIRS, MIFRS) and the Walter and Eliza Hall Institute of Medical Research (Edith Moffatt), grants from the Australian National Health and Medical Research Council (NHMRC) (a Project Grant #1043152 to A.M.J. and Project Grants #1145788, #1101405, Ideas Grant #1183070 and Fellowship #1141466 to J.E.V). This work was also made possible through the Australian Government National Health and Medical Research Council Independent Research Institutes Infrastructure Support Scheme and the Victorian State Government Operational Infrastructure Support.