Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Cell cycle and adhesion defects in mice carrying a targeted deletion of the integrin beta4 cytoplasmic domain.

The EMBO journal | Jul 15, 1998

http://www.ncbi.nlm.nih.gov/pubmed/9670011

The cytoplasmic domain of the integrin beta4 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 beta4 cytoplasmic domain. Analysis of homozygous mutant mice indicates that the tail-less alpha6beta4 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 p27(Kip). These findings indicate that the interactions mediated by the beta4 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.

Pubmed ID: 9670011 RIS Download

Mesh terms: Animals | Antigens, CD | Antigens, Surface | Basement Membrane | Cell Adhesion | Cell Adhesion Molecules | Cell Cycle | Cell Cycle Proteins | Cells, Cultured | Cyclin-Dependent Kinase Inhibitor p27 | Cytoplasm | Cytoskeleton | Desmosomes | Duodenum | Epidermolysis Bullosa, Junctional | Integrin alpha6beta4 | Integrin beta4 | Integrins | Intestinal Mucosa | Keratinocytes | Mice | Mice, Knockout | Microtubule-Associated Proteins | Pylorus | Sequence Deletion | Skin | Tumor Suppressor Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: P30-CA08748
  • Agency: NCI NIH HHS, Id: R01-CA58976

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.