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BRIEF REVIEWS P K AP M A C J F P B Plakoglobin (y-catenin), a member of the armadillo family ofproteins, is a constituent of the cytoplasrnic plaques of desmosomes and adher- ens junctions and is involved in anchorage of cytoskeletal filaments to specific cadhen”ns.When the plakoglobin gene is ablated in mice, ani- mals die between days 12 and 16 of embryogenesis owing to defects in heart function. Oflen, their heart ventricles burst, andpericardial tam- ponade appears to be the immediate cause of death. This tissue insta- bility correlates with the absence of desmosomes and a redistribution of desmosomal proteins in heart, but not in epithelial organs. Plakoglo- bin is an essential component of cardiac desmosomes and plays a cn..i- cial role in the architecture and stabilization of heart tissue. C 8 O Elsevier Science Inc. P ( i ac j d a a f d p a r a a a r i D a ( W v h Patricia Ruiz and Walter Birchmeier are at the Max-Delbriick Center for Molecular Med- icine, Berlin, Germany. * Address correspondence to: Dr. Patricia Ruiz, Center for Molecular Medicine, Max- DelbrLick Center, Robert-Rossle Str. 10, D- 13122 Berlin, Germany. TCM Vol. 8, 3, 1998 p W a g a t A M e K d p t m @ 1998,ElsevierScienceInc.,1050-1738/98/$19.00 a m p a a at C a a t 97

The Plakoglobin Knock-Out Mouse: A Paradigm for the Molecular Analysis of Cardiac Cell Junction Formation

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Page 1: The Plakoglobin Knock-Out Mouse: A Paradigm for the Molecular Analysis of Cardiac Cell Junction Formation

BRIEF REVIEWS

P KA P M A

C J FP B

Plakoglobin (y-catenin), a member of the armadillo family ofproteins,is a constituent of the cytoplasrnic plaques of desmosomes and adher-ens junctions and is involved in anchorage of cytoskeletal filaments tospecific cadhen”ns.When the plakoglobin gene is ablated in mice, ani-mals die between days 12 and 16 of embryogenesis owing to defects inheart function. Oflen, their heart ventricles burst, andpericardial tam-ponade appears to be the immediate cause of death. This tissue insta-bility correlates with the absence of desmosomes and a redistributionof desmosomal proteins in heart, but not in epithelial organs. Plakoglo-bin is an essential component of cardiac desmosomes and plays a cn..i-cial role in the architecture and stabilization of heart tissue.C 8 O Elsevier Science Inc.

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Patricia Ruiz and Walter Birchmeier are atthe Max-Delbriick Center for Molecular Med-icine, Berlin, Germany.*Address correspondence to: Dr. PatriciaRuiz, Center for Molecular Medicine, Max-DelbrLick Center, Robert-Rossle Str. 10, D-13122 Berlin, Germany.

TCM Vol. 8, 3, 1998

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Page 2: The Plakoglobin Knock-Out Mouse: A Paradigm for the Molecular Analysis of Cardiac Cell Junction Formation

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ph a of wild type and e) and plakoglobin –/– and embryos.

Note the reduced blood supply of pIakoglobin –/– embryos compared with control litter-mates, particularly in liver and placenta. The d f indicateblood flooding the pericardial cavity; the arrow in f points to a rupture in the left heartventricle in a plakoglobin –/– embryo. h and Ziindicate heart and liver, respectively; v and atindicate ventricle and atrium. (Adapted from Ruiz et al. 1996.)

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Page 3: The Plakoglobin Knock-Out Mouse: A Paradigm for the Molecular Analysis of Cardiac Cell Junction Formation

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signaling pathwayhas also been implicated in the develop-ment of cardiac tissue: signals from

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Page 4: The Plakoglobin Knock-Out Mouse: A Paradigm for the Molecular Analysis of Cardiac Cell Junction Formation

Adherens Junctions DesmosomesWrit/wingless

-,

Bodmer R: 1995. Heart development i~Dro-and its relationship to vertebrates.

Trends Cardiovasc Med 5:21-28.

I Bornslaeger EA, Corcoran CM, StappenbeckI TS, Green KJ: 1996. Breaking the connec-

-i- @esmoplakin>

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Developmental signaling pathways in heart formation. Functional and structural in-tegrity of cardiac tissue is guaranteed by intercalated discs, which consist of adherens junc-tions, desmosomes, and gap junctions. Plakoglobin (-y-catenin;in theonly junctional protein known to be present in both adherens junctions and desmosomes hasbeen involved in the wntiwingless signaling pathway. This pathway has also been implicated inthe development of cardiac tissue. Whether plakoglobin plays a dual role in the arrangementof junctional components as a structural and signaling molecule is discussed in the text.

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