Crosses of two independently derived transgenic mice demonstrate functional complementation of the genes encoding heavy (HLA-B27) and light (beta 2-microglobulin) chains of HLA class I antigens.

Abstract

In man a number of diseases are associated with certain alleles of MHC antigens. The most pronounced example is ankylosing spondylitis, which is strongly associated with HLA‐B27. As a first step towards a model system to study the basis of this association, transgenic mice were generated that showed cell surface expression of the HLA‐B27 antigen biochemically indistinguishable from HLA‐B27 antigen expressed on human cells. This result was obtained by crossing two independently derived strains of mice, one of which is transgenic for the HLA‐B27 heavy chain gene, and the other carrying and expressing the human beta 2m gene. Examination of HLA‐B27 and human beta 2m mRNA in various tissues shows the two genes to be expressed in a coordinate fashion. The mRNA levels follow those of endogenous H‐2 Class I genes.

Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2k) mice

“…In our B27 transgenic mouse model as well as in transgenic mouse models described by other investigators (26,(52)(53)(54)(55)(56), but unlike the findings in the B27 transgenic rat model (4)(5)(6), the transgenic mouse model studied by Weinreich et a1 (57), or the recently described model of HLA-B27 transgenic mice lacking P2m (58), no spontaneous or induced manifestation of disease occurs. It nevertheless provides a model suitable for defining a bacteria-specific CD8 immune response.…”

“…A 25-kb Sal I fragment of this clone containing the B*2705 gene was then used to establish the B*2705 transgenic mouse line. Founder mice containing 1 copy of the B*2705 gene were backcrossed to a human p,m-expressing transgenic mouse line (26). The double transgene B*2705hpzm was backcrossed onto CBA mice, and a stable double-transgenic mouse line established (21).…”

Misfolded major histocompatibility complex class I molecules accumulate in an expanded ER-Golgi intermediate compartment.

“…To obtain efficient expression at the cell surface of human class I molecules in transgenic mice, the simultaneous presence of the class I transgene and a human 132-microglobulin (h132m) transgene is required (Krimpenfort et al, 1987). We have described animals in which the HLA-B27 and h[32m gene were introduced on a single DNA fragment and where, consequently, these transgenes cosegregate (Baas, 1993).…”

The role of MHC class I heterodimer expression in mouse ankylosing enthesopathy

“…The ANKENT and SIA models have been described using different B27 transgenes (B*2702 and B*2705, respectively (Krimpenfort et al 1987;Nickerson et al 1990), as well as independently produced ko founders (Zijlstra et al 1989;Koller and Smithies 1989, respectively). Moreover, ANKENT and SIA have distinct pathological characteristics: nail changes, synovial inflammation, and phalangeal joint involvement are present in SIA (Khare et al 1995) but absent in ANKENT (Weinreich et al 1995a).…”

“…The establishment of β2m knockouts by homologous recombination (Zijlstra et al 1989) and doubly transgenic HLA-B*2702, hu-β2m mice has been described previously (Krimpenfort et al 1987). Mice were housed under conventional conditions.…”