PMID- 34793837
OWN - NLM
STAT- MEDLINE
DCOM- 20220126
LR  - 20220126
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 297
IP  - 6
DP  - 2021 Dec
TI  - CRISPR/Cas9-mediated SARM1 knockout and epitope-tagged mice reveal that SARM1 
      does not regulate nuclear transcription, but is expressed in macrophages.
PG  - 101417
LID - S0021-9258(21)01226-6 [pii]
LID - 10.1016/j.jbc.2021.101417 [doi]
LID - 101417
AB  - SARM1 is a toll/interleukin-1 receptor -domain containing protein, with roles 
      proposed in both innate immunity and neuronal degeneration. Murine SARM1 has been 
      reported to regulate the transcription of chemokines in both neurons 
      and macrophages; however, the extent to which SARM1 contributes to transcription 
      regulation remains to be fully understood. Here, we identify differential gene 
      expression in bone-marrow-derived macrophages (BMDMs) from C57BL/6 congenic 129 
      ES cell-derived Sarm1(-/-) mice compared with wild type (WT). However, we found 
      that passenger genes, which are derived from the 129 donor strain of mice that 
      flank the Sarm1 locus, confound interpretation of the results, since many of the 
      identified differentially regulated genes come from this region. To re-examine 
      the transcriptional role of SARM1 in the absence of passenger genes, here we 
      generated three Sarm1(-/-) mice using CRISPR/Cas9. Treatment of neurons from 
      these mice with vincristine, a chemotherapeutic drug causing axonal degeneration, 
      confirmed SARM1's function in that process; however, these mice also showed that 
      lack of SARM1 has no impact on transcription of genes previously shown to be 
      affected such as chemokines. To gain further insight into SARM1 function, we 
      generated an epitope-tagged SARM1 mouse. In these mice, we observed high SARM1 
      protein expression in the brain and brainstem and lower but detectable levels in 
      macrophages. Overall, the generation of these SARM1 knockout and epitope-tagged 
      mice has clarified that SARM1 is expressed in mouse macrophages yet has no 
      general role in macrophage transcriptional regulation and has provided important 
      new models to further explore SARM1 function.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Doran, Ciara G
AU  - Doran CG
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland.
FAU - Sugisawa, Ryoichi
AU  - Sugisawa R
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland.
FAU - Carty, Michael
AU  - Carty M
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland.
FAU - Roche, Fiona
AU  - Roche F
AD  - School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
FAU - Fergus, Claire
AU  - Fergus C
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland.
FAU - Hokamp, Karsten
AU  - Hokamp K
AD  - School of Genetics and Microbiology, Trinity College Dublin, Dublin 2, Ireland.
FAU - Kelly, Vincent P
AU  - Kelly VP
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland.
FAU - Bowie, Andrew G
AU  - Bowie AG
AD  - School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, 
      Trinity College Dublin, Dublin 2, Ireland. Electronic address: agbowie@tcd.ie.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211116
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Armadillo Domain Proteins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Epitopes)
RN  - 0 (SARM1 protein, mouse)
RN  - 5J49Q6B70F (Vincristine)
SB  - IM
MH  - Animals
MH  - *Armadillo Domain Proteins/biosynthesis/genetics
MH  - *CRISPR-Cas Systems
MH  - *Cytoskeletal Proteins/biosynthesis/genetics
MH  - *Epitopes/genetics/metabolism
MH  - *Gene Expression Regulation
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/metabolism
MH  - *Transcription, Genetic
MH  - Vincristine/metabolism
PMC - PMC8661062
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - SARM1
OT  - axon degeneration
OT  - chemokines
OT  - innate immunity
OT  - passenger genes
OT  - transcription
COIS- Conflict of interest The authors declare that they have no conflicts of interest 
      with the contents of this article.
EDAT- 2021/11/19 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/11/16
CRDT- 2021/11/18 20:13
PHST- 2021/08/28 00:00 [received]
PHST- 2021/11/03 00:00 [revised]
PHST- 2021/11/08 00:00 [accepted]
PHST- 2021/11/19 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/11/18 20:13 [entrez]
PHST- 2021/11/16 00:00 [pmc-release]
AID - S0021-9258(21)01226-6 [pii]
AID - 101417 [pii]
AID - 10.1016/j.jbc.2021.101417 [doi]
PST - ppublish
SO  - J Biol Chem. 2021 Dec;297(6):101417. doi: 10.1016/j.jbc.2021.101417. Epub 2021 
      Nov 16.