The cooperative effect of the Satin and Beige mutations in the suppression of NK and CTL activities in mice

Abstract

The functional activity of natural killer (NK) cells has been found to be modulated by several point mutations associated with coat color. The most commonly studied gene, beige (Bg), has been found to block a postrecognition event in the lytic cycle. Four other coat color mutations in the mouse (satin, leaden, fuzzy, pale ears) were studied for their effect on NK cell function, and only one, satin (Sa), was found to be suppressive. When both the Sa and Bg mutations were present in the same animal, their effects were synergistic in the suppression of NK levels. Normal numbers of NK cells were present in these double mutants, as determined by the frequency of IgG2b binding cells and by antiasialo GM1 staining. The ability of Sa/Bg NK cells to recognize and bind targets suggests that the defect is localized in the postbinding cytolytic pathway. These genes were not specific for NK cells and also suppressed alloimmune cytolytic T lymphocyte function. Since Sa/Bg mice are much more suppressed in NK function than Bg mice, we suggest that this double mutant may be a better model for NK deficiency in vivo.

The winged helix/forkhead transcription factor Foxq1 regulates differentiation of hair in satin mice

“…Furthermore, histological sections of the thymus and spleen showed no apparent structural defects in satin mice (data not shown). Thus, immune defects in satin mice, originally observed by McGarry et al (1984), is likely attributable to the 3H1 (C3H ϫ 101 hybrid strain) genetic background. It is possible that Foxq1 may have a minor effect in the maintenance of the immune system, and thus comprehensive functional analysis of the lymphocytes may be useful.…”

“…Consequently, the phenotype in sa/sa mice must arise from the failure to activate or repress a downstream signal required for keratinization. Interestingly, satin mice have been reported to exhibit suppressed NK-cell function and alloimmune cytotoxic T-cell function, a phenotype exacerbated by the effects of the closely linked beige (bg) gene product (McGarry et al, 1984). This hair/T-cell function may not be a chance association; a number of other mouse mutations that affect hair development also exhibit abnormal immune systems (Sundbert and King, 1996).…”

Forkhead transcription factors in immunology

“…Interestingly, the sa mutation confers a deficiency in natural killer cell activity but not numbers in vivo, an effect synergistic with the beige (bg, Lyst) mutation [153]. However, this effect may be strain specific [151] and has been studied predominantly in the presence of the bg mutation [153]. Thus, further investigation is warranted to determine the precise functions and mechanisms of Foxq1, not only in the immune system, but also in mammalian development and differentiation in general.…”

“…in vitro, Foxq1 can repress smooth muscle differentiation genes, such as telokin and SM22a [152], but whether these findings apply in vivo is not known definitively. Interestingly, the sa mutation confers a deficiency in natural killer cell activity but not numbers in vivo, an effect synergistic with the beige (bg, Lyst) mutation [153]. However, this effect may be strain specific [151] and has been studied predominantly in the presence of the bg mutation [153].…”

Expression, Genomic Structure and Mapping of the Thymus Specific Protease Prss16: A Candidate Gene for Insulin Dependent Diabetes Mellitus Susceptibility

“…Also within this conserved region in the mouse is the satin (sa) locus. sa is a mouse mutant with a mild immunodeficiency and a predisposition to developing lymphoproliferative disease [10].…”