Details

Autor(en) / Beteiligte

• Murgia, Chiara
• Blaikie, Pamela
• Kim, Nancy
• Dans, Michael
• Petrie, Howard T.
• Giancotti, Filippo G.

Titel

Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin β4 cytoplasmic domain

Ist Teil von

• The EMBO journal, 1998-07, Vol.17 (14), p.3940-3951

Ort / Verlag

Chichester, UK: John Wiley & Sons, Ltd

Erscheinungsjahr

1998

Link zum Volltext

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• The cytoplasmic domain of the integrin β4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein Shc. To examine the significance of these interactions during development, we have generated mice carrying a targeted deletion of the β4 cytoplasmic domain. Analysis of homozygous mutant mice indicates that the tail‐less α6β4 binds efficiently to laminin 5, but is unable to integrate with the cytoskeleton. Accordingly, these mice display extensive epidermal detachment at birth and die immmediately thereafter from a syndrome resembling the human disease junctional epidermolysis bullosa with pyloric atresia (PA‐JEB). In addition, we find a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin is reduced, and post‐mitotic enterocytes display increased levels of the cyclin‐dependent kinase inhibitor p27Kip. These findings indicate that the interactions mediated by the β4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell‐cycle control in the proliferative compartments of both stratified and simple epithelia.