DOI: 10.1073/pnas.092130099. Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1

Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1

10.1073/pnas.092130099

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Glutamate receptor-interacting protein 1 (GRIP1) is an adaptor protein composed of seven PDZ (postsynaptic density-95/Discs large/zona occludens-1) domains, capable of mediating diverse protein–protein interactions. GRIP1 has been implicated in the regulation of neuronal synaptic function, but its physiologic roles have not been defined in vivo . We find that elimination of murine GRIP1 results in embryonic lethality. GRIP1 −/− embryos develop abnormalities of the dermo-epidermal junction, resulting in extensive skin blistering around day 12 of embryonic life. Ultra-structural characterization of the blisters (or bullae) revealed cleavage of the dermo-epidermal junction below the lamina densa, an alteration reminiscent of the dystrophic form of human epidermolysis bullosa. Blisters were also observed in the lateral ventricle of the brain and in the meninges covering the cerebral cortex. These genetic data suggest that the GRIP1 scaffolding protein is required for the formation and integrity of the dermo-epidermal junction and reveal the importance of PDZ domains in the organization of supramolecular structures essential for mammalian embryonic development.

Authors 5

Friedhelm Bladt (first)
Anna Tafuri (additional)
Sigal Gelkop (additional)
Lowell Langille (additional)
Tony Pawson (additional)

References 35 Referenced 60

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:46 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 6:56 p.m.)
Indexed	3 months, 1 week ago (May 22, 2025, 5:29 a.m.)
Issued	23 years, 4 months ago (April 30, 2002)
Published	23 years, 4 months ago (April 30, 2002)
Published Online	23 years, 4 months ago (April 30, 2002)
Published Print	23 years, 3 months ago (May 14, 2002)

Funders 0

None

BibTeX

@article{Bladt_2002, title={Epidermolysis bullosa and embryonic lethality in mice lacking the multi-PDZ domain protein GRIP1}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.092130099}, DOI={10.1073/pnas.092130099}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Bladt, Friedhelm and Tafuri, Anna and Gelkop, Sigal and Langille, Lowell and Pawson, Tony}, year={2002}, month=apr, pages={6816–6821} }

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