MYD88

Model organisms

Model organisms have been used in the study of MYD88 function. The gene was originally discovered and cloned by Dan Liebermann and Barbara Hoffman in mice. In that species it is a universal adapter protein as it is used by almost all TLRs (except TLR 3) to activate the transcription factor NF-κB. Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK. It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease.

A conditional knockout mouse line, called Myd88^{tm1a(EUCOMM)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty-one tests were carried out on homozygous mutant animals, revealing one abnormality: male mutants had an increased susceptibility to bacterial infection.

Function

The human ortholog MYD88 seems to function similarly to mice, since the immunological phenotype of human cells deficient in MYD88 is similar to cells from MyD88 deficient mice. However, available evidence suggests that MYD88 is dispensable for human resistance to common viral infections and to all but a few pyogenic bacterial infections, demonstrating a major difference between mouse and human immune responses. Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of diffuse large B-cell lymphoma and Waldenstrom's macroglobulinemia.

Interactions

Myd88 has been shown to interact with:

Gene polymorphisms

Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified. and for some of them an association with susceptibility to various infectious diseases and to some autoimmune diseases like ulcerative colitis was found.