The in vivo expression of actin/salt-resistant hyperactive DNase I inhibits the development of anti-ssDNA and anti-histone autoantibodies in a murine model of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterised by the production of autoantibodies against ubiquitous antigens, especially nuclear components. Evidence makes it clear that the development of these autoantibodies is an antigen-driven process and that immune complexes involving DNA-containing antigens play a key role in the disease process. In rodents, DNase I is the major endonuclease present in saliva, urine and plasma, where it catalyses the hydrolysis of DNA, and impaired DNase function has been implicated in the pathogenesis of SLE. In this study we have evaluated the effects of transgenic overexpression of murine DNase I endonucleases in vivo in a mouse model of lupus. We generated transgenic mice having T-cells that express either wild-type DNase I (wt. DNase I) or a mutant DNase I ( ash. DNase I), engineered for three new properties - resistance to inhibition by G-actin, resistance to inhibition by physiological saline and hyperactivity compared to wild type. By crossing these transgenic mice with a murine strain that develops SLE we found that, compared to control nontransgenic littermates or wt. DNase I transgenic mice, the ash. DNase I mutant provided significant protection from the development of anti-single-stranded DNA and anti-histone antibodies, but not of renal disease. In summary, this is the first study in vivo to directly test the effects of long-term increased expression of DNase I on the development of SLE. Our results are in line with previous reports on the possible clinical benefits of recombinant DNase I treatment in SLE, and extend them further to the use of engineered DNase I variants with increased activity and resistance to physiological inhibitors.

Charitable giving: A test of a revised Theory of Planned Behaviour model

Recent world events aside, downward trends in donating behaviour in Australia have increased the need for research into the factors that inhibit and encourage charitable giving. A revised Theory of Planned Behaviour (TPB) model was used to determine the influence of attitudes, norms (injunctive, descriptive, and moral norms), perceived behavioural control (PBC), and past behaviour (PB) on intentions to donate money to charities and community service organisations. Respondents (N=186) completed a questionnaire assessing the constructs of the revised TPB model. Four weeks later, self-reported donating behaviour was assessed (n=65). Results showed support for the revised TPB model. Attitudes, PBC, injunctive norms, moral norms, and PB all predicted donating intentions. Descriptive norms did not predict intentions. Intention was the only significant predictor of selfreported behaviour four weeks later, with neither PBC nor PB having a direct effect on behaviour. Theoretical and applied implications of the results are discussed.