2015
EMBO J. 2015 Oct 1;34(19):2396-7. doi: 10.15252/embj.201592761.
Response to Heard et al.
Université Paris Sud, Paris, France; The University of Melbourne & La Trobe University, Melbourne, VIC, Australia; Ozgene Pty Ltd, Bentley, WA, Australia; University of Zürich, Zürich, Switzerland.
Service type: Knockout mice
Abstract
Heard et al (2015) generated cIap1−/− Xiap−/− mice and were surprised to find them to be viable and fertile, because we had reported (Moulin et al, 2012) that cIap1−/−Xiap−/− mice died by day E12.5 of embryogenesis (Moulin et al, 2012 Figs 1B and 2B and Supplementary Fig S1A). We are working with Heard et al (2015) in an attempt to determine why. It is, however, clear that failure of our cIap2FRT/FRTcIap1−/−Xiap−/− mice to survive past E12.5 is not due to non‐functional cIap2−/− genes. Three types of cross indicate that the cIap2FRT/FRT locus, which is carried by our cIap1−/− mice, does produce functional cIAP2. Firstly, comparison of the phenotypes of the cIap2FRT/FRTcIap1−/− mice, which are viable and fertile, with the cIap2−/−cIap1−/− mice, which die at E12.5, indicates that the cIap2FRT/FRT locus can function, at least to the extent needed to allow normal development when Xiap is present (Moulin et al, 2012). Secondly, when specific deletion of cIap1 in B cells was combined with whole body cIap2 deletion, it led to more profound B‐cell expansion than deletion of either IAP alone (Gardam et al, 2011). Thirdly, deletion of cIap1 in myeloid cells on either a cIap2−/− or cIap2−/− Xiap−/− background triggered splenomegaly, increased neutrophils and monocytes, inflammatory cytokine production and spontaneous inflammatory arthritis, whereas deletion of Xiap, cIap1 or cIap2 alone did not (Wong et al, 2014; Lawlor et al, 2015).
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