title: Establishment of Two Mouse Models for CEDNIK Syndrome Reveals the Pivotal Role of SNAP29 in Epidermal Differentiation.
abstract: Loss-of-function mutations in the synaptosomal-associated protein 29 (SNAP29) gene cause the cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome. In this study, we created total (Snap29(-/-)) as well as keratinocyte-specific (Snap29(fl/fl)/K14-Cre) Snap29 knockout mice. Both mutant mice exhibited a congenital distinct ichthyotic phenotype resulting in neonatal lethality. Mutant mice revealed acanthosis and hyperkeratosis as well as abnormal keratinocyte differentiation and increased proliferation. In addition, the epidermal barrier was severely impaired. These results indicate an essential role of SNAP29 in epidermal differentiation and barrier formation. Markedly decreased deposition of lamellar body contents in mutant mice epidermis and the observation of malformed lamellar bodies indicate severe impairments in lamellar body function due to the Snap29 knockout. We also found increased microtubule associated protein-1 light chain 3, isoform B-II levels, unchanged p62/SQSTM1 protein amounts, and strong induction of the endoplasmic reticulum stress marker C/EBP homologous protein in mutant mice. This emphasizes a role of SNAP29 in autophagy and endoplasmic reticulum stress. Our murine models serve as powerful tools for investigating keratinocyte differentiation processes and provide insights into the essential contribution of SNAP29 to epidermal differentiation.
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Goettingen, Goettingen, Germany.
authors.forename: Stina A
authors.initials: SA
authors.lastname: Schiller
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Goettingen, Goettingen, Germany; Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Seebode
authors.affiliation: Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Goettingen, Germany.
authors.forename: Georg L
authors.initials: GL
authors.lastname: Wieser
authors.affiliation: Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Goettingen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Goebbels
authors.affiliation: Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Goettingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Department of Cell Research and Immunology, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Mia
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Sarig
authors.affiliation: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
authors.affiliation: Department of Dermatology, Venereology and Allergology, University Medical Center Goettingen, Goettingen, Germany; Clinic for Dermatology and Venereology, University Medical Center Rostock, Rostock, Germany. Electronic address: steffen.emmert@med.uni-rostock.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007645:Keratoderma, Palmoplantar / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D020752:Neurocutaneous Syndromes / Q000235:genetics / Q000473:pathology*; D050766:Qb-SNARE Proteins / Q000235:genetics*; D050767:Qc-SNARE Proteins / Q000235:genetics*; D011897:Random Allocation; D012016:Reference Values
chemical_list: D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C486621:Snap29 protein, mouse