Lack of B Cell Leakiness in BALB/cA-nu, scid Double Mutant Mice.

Abstract

BALB/cA mice homozygous for both nu and scid mutations (BALB/cA-nu/nu, scid/scid) were developed by mating between BALB/cA-scid and BALB/cA-nu. These mice have greater longevity than C.B-17-scid because no thymic lymphoma occurs in them unlike in the latter. C.B-17-scid is known to show the leaky phenomenon in which a few clones of functional T and B cells develop in aged C.B-17-scid. Unexpectedly, the leaky B cells and T cells were absent or suppressed in BALB/cA-nu, scid mice when cytokine expressions were determined by RT-PCR, lymphocyte phenotypes by flow cytometry and serum immunoglobulin levels by ELISA. These results indicate that B cell leakiness may be induced by leaked T cells. BALB/cA-nu, scid mice may be useful as a recipient in allo-and xeno-transplantation experiments because of the absence of both thymic lymphomas and leakiness, in addition to lack of hair. Key words: leakiness, nude, scid mice and xenotransplantation because the mice lack functional T cells, but not B cells, resulting from lack of a thymus. Nude mice still have the advantage of hairlessness over SCID mice since observation of xenotransplants on the hairless skin is very easy. Therefore, double mutant mice with both scid and nu genes should be better recipients for xenotransplantation. We attempted to produce BALB/cA-nu/nu, scid/scid (nu, scid) mice which lack hair and both T and B cells. In addition, SCID mice have a high incidence of thymic lymphoma and an unresolved problem termed the leaky phenomenon in which oligoclonal T and B cells spon-

Immunodeficient NOD-scid IL-2R.GAMMA.null Mice Do Not Display T and B Cell Leakiness

“…1, Igs (IgG + IgM) at concentrations ranging between 1 and 10 µg/ml were detected in 15 (30 %) of 50 NOD-scid mice. These Ig levels were not considered representative of leakiness as they fell below the 10 µg/ml of serum Ig levels that define the leaky phenotype [5]. However, 121 of the NOG mice tested in the present study did not show detectable Igs.…”

“…A previous study by our group showed the absence of Ig production and T cell leakiness in BALB/cA-scid, nu mice [5]. The absence of leaky cells in these mice may be due to the lack of T cell development in the absence of a thymus.…”

“…The relationship between T cell leakiness and thymic lymphoma remains unclear. Previous work has shown that thymic lymphoma does not occur in BALB/ cA-scid, nu mice [5]; therefore, the growth and progression of thymic lymphoma in SCID mice may be a secondary effect of the leaked T cells, as speculated by Bosma et al [2]. The low incidence of thymic lymphoma observed in NOG mice could then be the result of the lack of T cell leakiness in these mice.…”

Platelet gene therapy corrects the hemophilic phenotype in immunocompromised hemophilia A mice transplanted with genetically manipulated human cord blood stem cells

“…It has been reported that such leakiness is higher in mice housed under nonspecific pathogen-free conditions, which is the type of facility in which we house our mice, and leakiness is generally higher on the C57BL/6 genetic background. [38][39][40] The FVIII null mice crossed with NSG mice were on a mixed genetic background of C57BL/6 and 129/SV, so NSGF8KO mice inherited a mixed genetic background of C57BL/6, 129/SV, and NOD. Backcrossing NSGF8KO mice to a pure NOD background will need to be pursued in future studies.…”

Induction of β-Defensin Expression by <i>Porphyromonas gingivalis</i>-Infected Human Gingival Graft Transplanted in <i>nu/nu</i> Mouse Subdermis

“…The native condition of human mucosal tissue was attenuated by this phenomenon. Tsukinoki et al [27] established a transplantation technique for normal human oral mucosa that does not exhibit cystic changes using immunodeficient nu/scid mice, which were derived from a cross of nu/nu mice and scid/scid mice [9, 26]. However, the transplantation of gingival tissue from periodontal diseases has yet to be established in common immunodeficient nu/nu or scid/scid mice.…”