title: Modeling AEC-New approaches to study rare genetic disorders.
abstract: Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare monogenetic disorder that is characterized by severe abnormalities in ectoderm-derived tissues, such as skin and its appendages. A major cause of morbidity among affected infants is severe and chronic skin erosions. Currently, supportive care is the only available treatment option for AEC patients. Mutations in TP63, a gene that encodes key regulators of epidermal development, are the genetic cause of AEC. However, it is currently not clear how mutations in TP63 lead to the various defects seen in the patients' skin. In this review, we will discuss current knowledge of the AEC disease mechanism obtained by studying patient tissue and genetically engineered mouse models designed to mimic aspects of the disorder. We will then focus on new approaches to model AEC, including the use of patient cells and stem cell technology to replicate the disease in a human tissue culture model. The latter approach will advance our understanding of the disease and will allow for the development of new in vitro systems to identify drugs for the treatment of skin erosions in AEC patients. Further, the use of stem cell technology, in particular induced pluripotent stem cells (iPSC), will enable researchers to develop new therapeutic approaches to treat the disease using the patient's own cells (autologous keratinocyte transplantation) after correction of the disease-causing mutations.
authors.affiliation: Department of Dermatology, University of Colorado School of Medicine, Aurora, Colorado; Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, Colorado; Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado School of Medicine, Aurora, Colorado; Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koch
authors.forename: Jason
authors.initials: J
authors.lastname: Dinella
authors.forename: Mary
authors.initials: M
authors.lastname: Fete
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Siegfried
authors.forename: Maranke I
authors.initials: MI
authors.lastname: Koster
mesh_terms: D000818:Animals; D002971:Cleft Lip / Q000235:genetics* / Q000473:pathology; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics* / Q000473:pathology; D005143:Eyelids / Q000002:abnormalities* / Q000473:pathology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000473:pathology; D009154:Mutation / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins
keywords: TP63; ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC); ectodermal dysplasia; genodermatoses; iPS cells; iPSC-based cell therapy; iPSC-derived keratinocytes; in vitro disease models; induced pluripotent stem cells; inherited skin disorders; skin equivalents