Cellular and animal models of skin alterations in the autism-related ADNP syndrome
Metadatos
Mostrar el registro completo del ítemEditorial
Springer Nature
Fecha
2019-01-24Referencia bibliográfica
Pilar, M., Oxana, K., Domingo, G. L., Adi, Z., Real, P., Illana, G., ... & Fernandez-Luna, J. L. (2019). Cellular and animal models of skin alterations in the autism-related ADNP syndrome. Scientific Reports (Nature Publisher Group), 9(1).
Patrocinador
This work was supported by grant CI14/09 from Fundacion Instituto de Investigacion Valdecilla to J.L.F.-L., PI14/00900 from Instituto de Salud Carlos III (ISCIII) to A.G., and AMN Foundation and ERA-NET Neuron to I.G.Resumen
Mutations in ADNP have been recently associated with intellectual disability and autism spectrum
disorder. However, the clinical features of patients with this syndrome are not fully identified, and
no treatment currently exists for these patients. Here, we extended the ADNP syndrome phenotype
describing skin abnormalities in both a patient with ADNP syndrome and an Adnp haploinsufficient
mice. The patient displayed thin dermis, hyperkeratotic lesions in periarticular areas and delayed wound
healing. Patient-derived skin keratinocytes showed reduced proliferation and increased differentiation.
Additionally, detection of cell cycle markers indicated that mutant cells exhibited impaired cell
cycle progression. Treatment of ADNP-deficient keratinocytes with the ADNP-derived NAP peptide
significantly reduced the expression of differentiation markers. Sonography and immunofluorescence
staining of epidermal layers revealed that the dermis was thinner in the patient than in a healthy
control. Adnp haploinsufficient mice (Adnp+/−) mimicked the human condition showing reduced dermal
thickness. Intranasal administration of NAP significantly increased dermal thickness and normalized
the levels of cell cycle and differentiation markers. Our observations provide a novel activity of the
autism-linked ADNP in the skin that may serve to define the clinical phenotype of patients with ADNP
syndrome and provide an attractive therapeutic option for skin alterations in these patients.