Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation

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Science  24 Aug 2018:
Vol. 361, Issue 6404, pp. 810-813
DOI: 10.1126/science.aar2641

Humans as models of human disease

Mice are a convenient model for exploring the functions of cellular signaling pathways. Occasionally, however, an “experiment of nature” highlights the perils of overreliance on mice. RIPK1 is a well studied protein kinase that regulates cell death. Mice deficient in RIPK1 die soon after birth because of the protein's widespread role in multiple tissues and organs. Cuchet-Lourenço et al. studied patients with inherited immunodeficiency of unknown cause (see the Perspective by Pasparakis and Kelliher). They identified inactivating mutations in the RIPK1 gene in four individuals. Unlike what has been seen in mice, the deleterious effects of RIPK1 loss in humans were confined to the immune system, a finding with potential therapeutic implications.

Science, this issue p. 810; see also p. 756

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