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In This Issue, The Journal of Immunology, Volume 173, Issue 2, July 2004, Pages 713–714, https://doi.org/10.4049/jimmunol.173.2.713
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Reversing the motheaten phenotype
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The Ostrowski laboratory previously demonstrated that the Ets2 transcription factor in macrophages from moth eaten mice is constitutively phosphorylated at Thr (aa 72). These mice carry the motheaten viable (me-v) mutation of the hemopoietic cell phosphatase gene (Hcphme-v/me-v) and suffer from an arthritis-like inflammation of the joints. In a paper from the same laboratory, Wei et al. (p. 1374 ), looked at the role of Ets2 phosphorylation in motheaten pathology. They introduced a mutated Ets2 gene encoding Ala at aa 72 into Hcphme-v/me-v mice. Mice homozygous for both genes (Ets2A72/A72 Hcphme-v/me-v) were similar to wild-type mice in having greater than six times the survival rate at 100 days, twice the body weight, and no joint inflammation compared with Hcphme-v/me-v homozygotes. Whereas the Hcphme-v/me-v animals developed fatal pneumonitis from an accumulation of macrophages and neutrophils in their lungs, the double homozygotes did not accumulate macrophages in their lungs and remained healthy. However, bone marrow-derived macrophages from the double homozygotes lost some of the apoptotic resistance of Hcphme-v/me-v macrophages. A number of inflammation-related genes expressed in alveolar and peritoneal macrophages from Hcphme-v/me-v mice were found by quantitative real time PCR to be down-regulated in macrophages from the double homozygotes. The authors propose that Hcph negatively regulates Ets2 phosphorylation; constitutive phosphorylation of Ets2 in motheaten mice results in increased expression of genes responsible for the severe inflammatory phenotype.
