Brazilian Blood-Suckers
Fogo selvagem (FS) is mediated by pathogenic antibodies to desmoglein-1 (Dsg1). Diaz et al searched for anti-Dsg1 antibodies in the Amerindian Terena population of Limão Verde, Brazil. They compared the sera of patients with leishmaniasis, Chagas and onchocerciasis (diseases with insect vectors) to leprosy and South American blastomycosis (without vectors) and to normal controls. A significant number of patients with insect transmitted diseases had anti-Dsg1 antibodies, yet none had FS. Did immunizing antigens originate from insect saliva as well as the pathogenic organism researched? Establishing the mechanism would identify susceptibility factors and potential novel preventive mechanisms for FS's devastating skin blisters and erosions. J Invest Dermatol 123:1045–1051, 2004.
Taking Tsk to Task
Tight skin (Tsk) mouse is a model for dermal fibrosis in scleroderma. In both the model and systemic sclerosis patients, skin becomes tethered to underlying tissues. Lemaire and colleagues proposed that altered binding of fibulins to fibrillin-associated proteins could mediate the effect of Tsk fibrillin-1 on elastic fiber formation in the skin. Their findings reveal that mutant Tsk fibrillin-1 markedly changes the association of fibulin-2 and fibulin-5 with fibrillin-1 in hypodermal connective tissue matrices. These interactions might cause skin tethering in Tsk mice and alter the regulation of elastogenesis. J Invest Dermatol 123:1063–1069, 2004.
Of Mice and Men
Primary cultures of mouse and human keratinocytes (KCs) are used to study proliferation, differentiation, and transformation in skin. The mouse-study findings are then extrapolated to human diseases. Chaturvedi and colleagues, making direct comparisons, suggest remarkably different senescent and apoptotic tendencies and vulnerabilities between murine and human KCs. Molecular regulators of human KCs involve the p53 gene, but other mediators besides p53 may also account for phenotypic differences. These studies warrant caution when using mouse KCs in vitro and extrapolating from mouse models to some human skin disorders; many other factors could cause different responses to apoptotic induction. J Invest Dermatol 123:1200–1203, 2004.
Scales and SLS
Sjögren–Larsson syndrome (SLS), an autosomal recessive disorder, is characterized by congenital ichthyosis, mental retardation and spastic paresis. Since 1996 it has been known that mutations in the fatty aldehyde dehydrogenase (FALDH) gene (ALDH3A2) lead to SLS. Recently, however, in both the 6-year-old sister and 1-year-old brother with SLS in a Japanese family, Shibaki and coworkers detected a combination of heterozygous mutations in exon 4 (present in their mother) and exon 7 (present in their father). Their investigations now more precisely reveal that ALDH3A2 mutations lead to the defective lamellar granule contents and defective intercellular lipids of SLS's scaly skin. J Invest Dermatol 123:1197–1199, 2004.
