title: Palmoplantar Keratoderma in Slurp2-Deficient Mice.
abstract: 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.
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Allan
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Shiri
authors.initials: S
authors.lastname: Procaccia
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Deanna
authors.initials: D
authors.lastname: Tran
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Barnes
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Mikael
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California, USA.
authors.forename: Bernard B
authors.initials: BB
authors.lastname: Allan
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Lorraine C
authors.initials: LC
authors.lastname: Young
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Howard Hughes Medical Institute, University of California, Los Angeles, California, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hong
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Howard Hughes Medical Institute, University of California, Los Angeles, California, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. Electronic address: lfong@mednet.ucla.edu.
authors.forename: Loren G
authors.initials: LG
authors.lastname: Fong
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, California, USA. Electronic address: sgyoung@mednet.ucla.edu.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.affiliation: Department of Medicine, Divisions of Cardiology and Dermatology, David Geffen School of Medicine, University of California, Los Angeles, California, USA. Electronic address: abeigneux@mednet.ucla.edu.
authors.forename: Anne P
authors.initials: AP
authors.lastname: Beigneux
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D002478:Cells, Cultured; D018389:Codon, Nonsense; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000172:deficiency / Q000235:genetics*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D018389:Codon, Nonsense; D058851:GPI-Linked Proteins; C485626:LYNX1 protein, human; C545249:SLURP-1 protein, mouse; D014568:Urokinase-Type Plasminogen Activator