PHENOTYPIC AND MOLECULAR CHARACTERIZATION OF A NOVEL P63ALPHA;KO MOUSE MODEL

The transcription factor p63, a p53 gene family member, plays a crucial role in embryonic development of stratified epithelia where it can function either as an activator or a repressor. In the epidermis, p63 is a master regulator of epidermal gene expression and is crucial for cell proliferation, cell adhesion and stratification. Here we describe a new p63α-/- mouse model in which we delete exon 13 leading to the expression of the p63β isoform. Newborn p63α-/- mice die soon after birth and are characterised by cleft palate and digit malformations but exhibit normal skin. Our study indicates that p63α and p63β are not interchangeable in palate and limb development during embryogenesis, whereas expression of either one allows normal skin development, laying the foundation for a better understanding of the contribution of each p63 isoforms to mouse development. Compared to previously generated p63 knock-out mice, morphological and molecular impairment in p63α-/- model are mainly caused by alterations in the expression of genes involved in cell-cell and cell-matrix interactions. Taken together, these novel findings shed light on the function of both the alpha and the beta isoforms, and indicate that p63α is specifically required for limb and palate development, whereas p63β can replace p63α in skin development and in the adulthood.