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

Autor: Heather E. Stefanski, Yan Xing, Jemma Nicholls, Leslie Jonart, Emily Goren, Patricia A. Taylor, Alea A. Mills, Megan Riddle, John McGrath, Jakub Tolar, Georg A. Hollander, Bruce R. Blazar
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Gene Knockout Techniques
Mice
White Blood Cells
Spectrum Analysis Techniques
Animal Cells
Medicine and Health Sciences
Promoter Regions
Genetic
Skin
Mice
Knockout
Thymocytes
Multidisciplinary
integumentary system
T Cells
Stem Cells
Genetically Modified Organisms
Forkhead Transcription Factors
Flow Cytometry
Thymus
Spectrophotometry
Engineering and Technology
Medicine
Cytophotometry
Cellular Types
Anatomy
Integumentary System
Genetic Engineering
Research Article
Biotechnology
Hematopoietic Progenitor Cells
Immune Cells
Science
Immunology
Cytotoxic T cells
Bioengineering
Thymus Gland
Research and Analysis Methods
Hair Follicles
Animals
Blood Cells
Genetically Modified Animals
Biology and Life Sciences
Alopecia
Cell Biology
stomatognathic diseases
Immune System
Trans-Activators
sense organs
Gene Deletion
Hair
Zdroj: PLoS ONE, Vol 17, Iss 1, p e0261770 (2022)
PLoS ONE, Vol 17, Iss 1 (2022)
PLoS ONE
PLoS ONE, 17 (1)
ISSN: 1932-6203
Popis: 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.
PLoS ONE, 17 (1)
ISSN:1932-6203
Databáze: OpenAIRE
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