Abstract

This proposal outlines experiments designed to further understand the molecular structure and function of two classes of intercellular junctions, gap junctions and tight junctions. There are five specific aims. First, the investigators will use Cx37 -/- transgenic mice to study the signalling between granulosa and oocyte, and assess the role of cAMP in meiosis. Second, they will use KO Cx37 and KO Cx40 animals to study the role of those connexins on endothelial function. Third, the maternally inherited mRNA coding for Cx38 will be ablated and the developmental consequences to embryos will be studied. Fourth, dominant negative mutants of occludin, ZO1 and ZO2 will be used to study the role of those proteins in the Xenopus embryo. Finally, as a fifth specific aim, the possible role of Cx33 in a form of CMTX associated with mental retardation will be studied, and Cx33 KO mice will be generated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM018974-29
Application #
6138287
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Program Officer
Shapiro, Bert I
Project Start
1975-01-01
Project End
2001-12-31
Budget Start
2000-01-01
Budget End
2000-12-31
Support Year
29
Fiscal Year
2000
Total Cost
$384,658
Indirect Cost

  Institution

Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Magnotti, Laura M; Goodenough, Daniel A; Paul, David L (2011) Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality. Glia 59:1064-74
Magnotti, Laura M; Goodenough, Daniel A; Paul, David L (2011) Functional heterotypic interactions between astrocyte and oligodendrocyte connexins. Glia 59:26-34
Altevogt, Bruce M; Paul, David L (2004) Four classes of intercellular channels between glial cells in the CNS. J Neurosci 24:4313-23
Menichella, Daniela M; Goodenough, Daniel A; Sirkowski, Erich et al. (2003) Connexins are critical for normal myelination in the CNS. J Neurosci 23:5963-73
Altevogt, Bruce M; Kleopa, Kleopas A; Postma, Friso R et al. (2002) Connexin29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems. J Neurosci 22:6458-70
Bruzzone, R; White, T W; Paul, D L (1994) Expression of chimeric connexins reveals new properties of the formation and gating behavior of gap junction channels. J Cell Sci 107 ( Pt 4):955-67
Bruzzone, R; White, T W; Scherer, S S et al. (1994) Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease. Neuron 13:1253-60
Musil, L S; Goodenough, D A (1993) Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell 74:1065-77
Bruzzone, R; Haefliger, J A; Gimlich, R L et al. (1993) Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 4:7-20
Flint, K K; Rosbash, M; Hall, J C (1993) Transfer of dye among salivary gland cells is not affected by genetic variations of the period clock gene in Drosophila melanogaster. J Membr Biol 136:333-42

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