Myd88 Conditional Knockout mouse models

Myd88, the mouse ortholog of human MYD88, encodes the universal TIR domain adaptor for every Toll-like receptor except TLR3 and for IL-1R, IL-18R, and IL-33R, using its death domain to nucleate a helical Myddosome with IRAK4 and IRAK1 or IRAK2 that activates TRAF6, TAK1, IKK, and MAPK signaling. Human MYD88 deficiency yields severe pyogenic bacterial infection with otherwise intact immunity, while the recurrent L265P substitution in the TIR domain drives spontaneous Myddosome assembly and constitutive NF-kB in Waldenstrom macroglobulinemia and activated B cell diffuse large B cell lymphoma, cooperating with CD79B in a B cell receptor associated supercomplex. This split biology dictates the allele fork precisely: a conditional null tests requirement for innate sensing, and an L265P knockin, ideally Cd19-Cre or Aicda-Cre restricted and inducible, models the lymphoma. Since germline null phenotypes are strongly microbiota dependent, use littermate controls and defined flora rather than cross-facility comparisons.

Myd88 conditional knockout mice carry a floxed allele so you delete function only where Cre is active. The germline allele stays intact until you cross to a tissue specific Cre. Labs reach for this design when a global knockout is lethal, when they need adult onset loss, or when regional redundancy hides a whole body phenotype.