P63 targeted deletion under the FOXN1 promoter disrupts pre-and post-natal thymus development, function and maintenance as well as induces severe hair loss

• Published in: PloS one Vol. 17; no. 1; p. e0261770
• Main Authors: Stefanski, Heather E, Xing, Yan, Nicholls, Jemma, Jonart, Leslie, Goren, Emily, Taylor, Patricia A, Mills, Alea A, Riddle, Megan, McGrath, John, Tolar, Jakub, Hollander, Georg A, Blazar, Bruce R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-01-2022; Public Library of Science (PLoS)
• Subjects: Aging; Alopecia; Alopecia - genetics; Alopecia - metabolism; Animals; Antibodies; Apoptosis; Atrophy; Baldness; Biology and Life Sciences; Defects; Dermatology; Development; Embryo cells; Embryogenesis; Engineering and Technology; Epithelial cells; Epithelium; Fetus; Flow cytometry; Follicles; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Deletion; Gene Knockout Techniques; Genetic aspects; Growth; Hair; Health aspects; Hypoplasia; Immune response; Immunological deficiency syndromes; Infants; Laboratories; Lethality; Lymphocytes; Lymphocytes T; Lymphopenia; Maintenance; Medicine and Health Sciences; Mice; Mice, Knockout; Morphogenesis; Neonates; Pediatric research; Pediatrics; Physiological aspects; Promoter Regions, Genetic; Research and Analysis Methods; Risk factors; Skin; Stem cell transplantation; Stem cells; Thymic hypoplasia; Thymus; Thymus gland; Thymus Gland - growth & development; Trans-Activators - deficiency; Trans-Activators - metabolism; Transcription factors; United States; Minneapolis Minnesota; New York; United States > US; Switzerland; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0261770

Progressive immune deficiency of aging is characterized by severe thymic atrophy, contracted T cell repertoire, and poor immune function. p63 is critical for the proliferative potential of embryonic and adult stem cells, as well as thymic epithelial cells (TECs). Because p63 null mice experience rapid post-natal lethality due to epidermal and limb morphogenesis defects, studies to define a role for p63 expression in TEC biology focused on embryonic thymus development and in vitro experiments. Since post-natal thymic stromal development and function differs from that of the embryo, we assessed the impact of lineage-restricted p63 loss on pre- and post-natal murine TEC function by generating mice with a loss of p63 function targeted to TEC, termed p63TECko mice. In adult p63TECko mice, severe thymic hypoplasia was observed with a lack in a discernable segregation into medullary and cortical compartments and peripheral T cell lymphopenia. This profound thymic defect was seen in both neonatal as well as embryonic p63TECko mice. In addition to TECs, p63 also plays in important role in the development of stratified epithelium of the skin; lack of p63 results in defects in skin epidermal stratification and differentiation. Interestingly, all adult p63TECko mice lacked hair follicles despite having normal p63 expression in the skin. Together our results show a critical role of TEC p63 in thymic development and maintenance and show that p63 expression is critical for hair follicle formation.