Female and male mice, we also determine an unanticipated function for
Female and male mice, we also determine an unanticipated function for PR in generating and/or sustaining sexual dimorphism in splenic leukocyte abundance in this model.Author Manuscript Author Manuscript Benefits Author Manuscript Author ManuscriptPR deficiency increases IgG autoAb production in aged female, but not male, Nba2 mice Simply because we had previously observed that PR deficiency in non-autoimmune mice resulted in enhanced IgG Ab responses to TD immunization (28), we Wnt3a Surrogate, Human (HEK293, Fc) hypothesized that we would observe elevated IgG, but not IgM, autoAb FLT3 Protein Formulation levels in Nba2.PR-/- mice. B6.PR-/- mice, generated in our lab and described in ref. (28), had been crossed Nba2 mice to produce Nba2.PR+/- breeding pairs. Subsequent litters showed Mendelian or near-Mendelian distribution PR-/- mutation among male and female pups (data not shown). We then observed PR+/+ and PR-/- mice from various litters for 10 mo., measuring serum autoAb levels just about every two mo. starting at age 4 mo. We chose to measure serum anti-chromatin reactivity as a result of comparatively high penetrance of this phenotype amongst aged female Nba2 mice (34). The assay we applied detected Ig with reactivity to chromatin and its individual components, histones and DNA (35). Among the 25 animals observed, only one spontaneous death occurred: a 9-mo-old male PR+/+ mouse that was identified dead in its cage from unknown causes. Amongst female mice, loss of PR did not appreciably have an effect on median serum anti-chromatin IgM levels at any time point, although two PR-/- mice showed higher levels at 8 and 10 mo. (Fig. 1A). In contrast, from six mo. onward, most PR-/- female mice showed greater IgG1 and IgG2c autoAb levels than the median value for sex-matched controls. The differences in median values had been statistically considerable at 6 mo. (IgG1) and eight mo. (IgG2c) (Fig. 1A). To improved estimate autoAb production throughout the life of every single animal, we calculated cumulative autoAb production by summing all values for each animal as much as six, eight or ten mo.Autoimmunity. Author manuscript; available in PMC 2016 April ten.Wong et al.Pageand calling this sum area beneath curve (AUC). PR deficiency had no statistically significant impact on imply IgM or IgG1 autoAb AUC at any time point (Fig. 1B and data not shown). Nonetheless, PR deficiency increased IgG2c autoAb AUC levels amongst female mice at eight and ten mo. (Fig. 1B). These increases couldn’t be explained by enhanced total serum IgG2c levels (Fig. 1C). PR deficiency did, nonetheless, result in a slight but statistically substantial decrease in imply total serum IgM levels in female mice at 10 mo. With each other, these final results indicate that PR can suppress or delay the emergence of class-switched IgG2c and IgG1 autoAbs in aged female Nba2 mice. Related effects of PR on IgG autoAb production had been not observed in aged male mice (Figs. 1A 1C). However, at ten mo., male PR-/- showed higher median IgM autoAb levels than did sex-matched controls (Fig. 1A). Amongst PR+/+ controls, female mice showed larger anti-chromatin and total IgM than male mice, and these variations were statistically important at ten mo. (Figs. 1A 1C). Related differences have been not observed for either total or anti-chromatin IgG1 and IgG2c. PR deficiency may well influence glomerular IC deposition in aged Nba2 mice In female NZB/W mice, the Nba2 locus is crucial for complete expression of anti-chromatin Abs and IC-mediated GN (34, 36). Simply because PR loss elevated levels of circulating IgG autoAbs in female mice (Figs. 1A and 1B), we examined kidneys at ten mo. for increas.
