Allan Christopher M, Procaccia Shiri, Tran Deanna, Tu Yiping, Barnes Richard H, Larsson Mikael, Allan Bernard B, Young Lorraine C, Hong Cynthia, Tontonoz Peter, Fong Loren G, Young Stephen G, Beigneux Anne P
Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Department of Molecular Biology, Genentech, South San Francisco, California, USA.
J Invest Dermatol. 2016 Feb;136(2):436-443. doi: 10.1016/j.jid.2015.11.003. Epub 2015 Nov 18.
SLURP1, a member of the lymphocyte antigen 6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. SLURP2, another secreted lymphocyte antigen 6 protein, is encoded by a gene located ?20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2-3 sequences had been replaced with lacZ and neo cassettes. Slurp2(-/-) mice exhibited hyperkeratosis on the volar surface of the paws (i.e., palmoplantar keratoderma), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are similar to those of Slurp1(-/-) mice. To solidify a link between Slurp2 deficiency and palmoplantar keratoderma and to be confident that the disease phenotypes in Slurp2(-/-) mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X(-/-)) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X(-/-) mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.
SLURP1是淋巴细胞抗原6蛋白家族的成员之一，由基底层上方的角质形成细胞分泌。SLURP1的突变会导致一种掌跖角化病（PPK），即梅勒达病。SLURP2是另一种分泌型淋巴细胞抗原6蛋白，由位于SLURP1下游约20 kb处的一个基因编码。SLURP2由基底层上方的角质形成细胞产生。为了研究SLURP2的重要性，我们首先检查了Slurp2基因敲除小鼠，这些小鼠的外显子2 - 3序列已被lacZ和neo盒取代。Slurp2(-/-)小鼠在爪的掌面出现角化过度（即掌跖角化病）、角质形成细胞增殖增加以及角质层中脂滴积累。它们还表现出体重减轻和后肢紧握。这些表型与Slurp1(-/-)小鼠的表型相似。为了巩固Slurp2缺陷与掌跖角化病之间的联系，并确保Slurp2(-/-)小鼠的疾病表型不是由于lacZ和neo盒对Slurp1表达的影响所致，我们创建了一个新的Slurp2基因敲除小鼠品系（Slurp2X(-/-)），其中Slurp2通过一个简单的无义突变失活。Slurp2X(-/-)小鼠表现出相同的疾病表型。因此，Slurp2缺陷和Slurp1缺陷会导致相同的疾病表型。
