B6.129p2 sjl myd88tm1defr j

BL/10 (stock# 000666) and NOD.B10 (stock# 002591) mice are available from Jackson Laboratories. Generation and validation of pSS conditional knockout mice that lack Myd88 in the hematopoietic compartment, referred to as NOD.B10^Myd88Δ, were described previously (25 (link)). Briefly, we first generated NOD.B10 mice that expressed Cre recombinase under the control of the Vav promoter (B6-Tg(vav1-icre)A2Kio/J) (Jackson Labs stock #008610) (29 (link), 30 (link)). We then bred Myd88 floxed animals (B6.129P2(SJL)-Myd88^tm1Defr/J) (Jackson Labs stock # 008888) to the NOD.B10 strain (Jackson Labs stock #002591) (31 (link)) to generate NOD.B10^Myd88fl/fl mice. Animals were backcrossed to the NOD.B10 strain for at least 6 generations and were verified to be fully congenic using a speed congenics approach (Jackson Laboratories). We then bred NOD.B10^Cre-Vav animals to the NOD.B10^Myd88fl/fl strain and the resultant progeny that expressed the Cre transgene under the control of the Vav promoter were designated as NOD.B10^Myd88Δ. Littermates that did not express the Cre transgene (NOD.B10^Myd88fl/fl) were employed as controls (25 (link)).
All animals used were females that were at least 26 weeks of age, the time at which the animals develop clinical disease (26 (link), 27 (link)). All animal experiments were carried out in accordance with IACUC and NIH guidelines.

Founder mice utilized in this study were purchased from The Jackson Laboratory (Bar Harbor, Maine) and included the following strains: C57BL/6J (Cat #000664), B6.129S7-Rag1tm1Mom/J (RAG1 Knockout (KO), Cat # 002216), B6.Cg-Tg(TcraTcrb)425Cbn/J (OT-II, Cat # 004194), B6.129S2-Cd4tm1Mak/J (CD4 KO, Cat# 002663), B6.129S7-Il1r1^tm1Imx/J (IL-1R KO, Cat# 003245), B6.129P2-Lyz2tm1(cre)Ifo/J (Lyz2-Cre, Cat # 004781), B6.Cg-Tg(Cd4-cre)1Cwi/BfluJ (CD4-Cre, Cat # 022071) and B6.129P2(SJL)-Myd88tm1Defr/J (MyD88^Flox/Flox, Cat # 008888). While CD4-Cre.MyD88^Flox/Flox conditional KO mice were generated by crossing CD4-Cre mice with MyD88^Flox/Flox mice (resulting in Cre-mediated excision of MyD88 in CD4+ as well as CD8+ T-cells), Lyz2-Cre.MyD88^Flox/Flox conditional KO mice were produced by crossing Lyz2-Cre mice with MyD88 ^Flox/Flox mice—resulting in excision of MyD88 in cells of myeloid lineage. For each strain, F1 WT/Cre-WT/FL mice were crossed to produce WT/Cre-FL/FL mice. Backcrossing of F1 WT/Cre-FL/FL mice to WT/WT-FL/FL mice yielded additional WT/Cre-FL/FL experimental mice. All mice were genotyped prior to breeding/experimental use. Mice were provided with food and water ad libitum and housed in specific pathogen free mouse facilities under IACUC-approved protocols (University of Pittsburgh, Pittsburgh, PA).