title: Regulation by non-major histocompatibility complex genes of the allo-4-hydroxy-phenylpyruvate dioxygenase (F liver protein) response.
abstract: Although rapid progress is being made in the quantitative genetics of multifactorial disease, no response to a simple antigen has yet been subjected to full genomic analysis. The well-characterized antigen allo-HPPD (4-hydroxy-phenylpyruvate dioxygenase, previously known as F liver antigen) is a good candidate for such treatment. Old and new data bearing on this possibility are here assembled. In respect of antibody production and an early burst of interleukin-4 (IL-4) transcription, introduction of the non-major histocompatibility complex (MHC) background from A/J strain mice into F1 hybrids with C57BL10 strains up-regulates the response. These findings can be aligned with previous quantitative genetics carried out on airway hyper-responsiveness in related strains, and to a lesser extent with the genetics of autoimmune diabetes in the mouse. Taken together, the findings suggest that regulation of the pro-inflammatory cytokines are largely responsible for the variation. Additional data indicate that these non-MHC genes are are to a variable extent (depending on the response parameter) epistatic to the down-regulatory MHC allele H-2Ab.
authors.affiliation: Cancer Research Laboratories, University of California at Berkeley, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Brunner
authors.forename: N A
authors.initials: NA
authors.lastname: Mitchison
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D001249:Asthma / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4; D015111:4-Hydroxyphenylpyruvate Dioxygenase