biostudies-literatureAlmeida FFLOEWE Center for Cell and Gene Therapy GermanyNational Health and Medical Research Council AustraliaGOIN postdoc fellowship Frankfurt Germanye1475875https://www.ebi.ac.uk/biostudies/studies/S-EPMC6169588biostudies-literatureUnknown7(10)NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCR^B6C14R strain. Ly5.1^C14R NK cells expressed similar levels of <i>Ncr1</i> mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors <i>in vivo</i>. Expression of the mutant NKp46^C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1^C14R mice had normal number of NK cells, tOncoimmunologyA point mutation in the <i>Ncr1</i> signal peptide impairs the development of innate lymphoid cell subsets.PMC6169588PCOFUND-GA-2011-29177610549251124907III L 4-518/17.004Ullrich EMarcais ASchleicher UUgolini SKalensee FAlmeida FFShi WFirth MHerold MJKoch JWillis SNLuong KZoller TGalluso JLiao YBelz GTGiannattasio AMercier FESpallotta FKueh AJNarni-Mancinelli EWalzer TRais BWeil SFaure FTognarelli SScadden DTSteinle AHuntington NDChiocchetti AGFriede MEVivier EfalseA point mutation in the <i>Ncr1</i> signal peptide impairs the development of innate lymphoid cell subsets.NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCR^B6C14R strain. Ly5.1^C14R NK cells expressed similar levels of <i>Ncr1</i> mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors <i>in vivo</i>. Expression of the mutant NKp46^C14R in 293T cells showed that NKp46 protein trafficking to the cell surface was compromised. Although Ly5.1^C14R mice had normal number of NK cells, t2018-01-01T00:00:00Z20182026-04-30T22:40:29.397Z2019-03-26T23:59:12ZS-EPMC61695883028834210.1080/2162402X.2018.1475875