@article{839f451bb2cd4ab18d437fbcf816c13a,
title = "Passenger Mutations Confound Phenotypes of SARM1-Deficient Mice",
abstract = "The Toll/IL-1R-domain-containing adaptor protein SARM1 is expressed primarily in the brain, where it mediates axonal degeneration. Roles for SARM1 in TLR signaling, viral infection, inflammasome activation, and chemokine and Xaf1 expression have also been described. Much of the evidence for SARM1 function relies on SARM1-deficient mice generated in 129 ESCs and backcrossed to B6. The Sarm1 gene lies in a gene-rich region encompassing Xaf1 and chemokine loci, which remain 129 in sequence. We therefore generated additional knockout strains on the B6 background, confirming the role of SARM1 in axonal degeneration and WNV infection, but not in VSV or LACV infection, or in chemokine or Xaf1 expression. Sequence variation in proapoptotic Xaf1 between B6 and 129 results in coding changes and distinct splice variants, which may account for phenotypes previously attributed to SARM1. Reevaluation of phenotypes in these strains will be critical for understanding the function of SARM1.",
keywords = "SARM1, TLR signaling, Wallerian degeneration, Xaf1, chemokines, viral infection",
author = "Uccellini, {Melissa B.} and Bardina, {Susana V.} and S{\'a}nchez-Aparicio, {Maria Teresa} and White, {Kris M.} and Hou, {Ying Ju} and Lim, {Jean K.} and Adolfo Garc{\'i}a-Sastre",
note = "Funding Information: This work was partially supported by R01AI108715 to J.K.L. The mice used for this study were produced by the Mouse Genetics and Gene Targeting Center of Research Excellence (CoRE), which is supported by the Icahn School of Medicine at Mount Sinai and a Cancer Center Support Grant (1P30CA196521-01) from the National Cancer Institute/National Institutes of Health. We thank William Janssen at the Microscopy CoRE and Advanced Bioimaging Center for assistance with nerve imaging. We thank Michael Diamond and Andrew Pekosz for reagents and Zuleyma Peralta and Maryline Panis for technical assistance. Conceptualization & Methodology, M.B.U. and A.G.-S.; Investigation, M.B.U. S.V.B. M.T.S.-A. K.M.W. and Y.-J.H.; Resources, J.K.L.; Writing, M.B.U.; Supervision, A.G.-S. The authors declare no competing interests. Funding Information: This work was partially supported by R01AI108715 to J.K.L. The mice used for this study were produced by the Mouse Genetics and Gene Targeting Center of Research Excellence (CoRE), which is supported by the Icahn School of Medicine at Mount Sinai and a Cancer Center Support Grant ( 1P30CA196521-01 ) from the National Cancer Institute/National Institutes of Health . We thank William Janssen at the Microscopy CoRE and Advanced Bioimaging Center for assistance with nerve imaging. We thank Michael Diamond and Andrew Pekosz for reagents and Zuleyma Peralta and Maryline Panis for technical assistance. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = apr,
day = "7",
doi = "10.1016/j.celrep.2020.03.062",
language = "English",
volume = "31",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}