title: Targeted disruption of the murine zyxin gene.
abstract: Zyxin is an evolutionarily conserved protein that is concentrated at sites of cell adhesion, where it associates with members of the Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) family of cytoskeletal regulators and is postulated to play a role in cytoskeletal dynamics and signaling. Zyxin transcripts are detected throughout murine embryonic development, and the protein is widely expressed in adults. Here we used a reverse genetic approach to examine the consequences of loss of zyxin function in the mouse. Mice that lack zyxin function are viable and fertile and display no obvious histological abnormalities in any of the organs examined. Because zyxin contributes to the localization of Ena/VASP family members at certain subcellular locations, we carefully examined the zyxin(-/-) mice for evidence of defects that have been observed when Ena/VASP proteins are compromised in the mouse. Specifically, we evaluated blood platelet function, nervous system development, and skin architecture but did not detect any defects in these systems. Zyxin is the founding member of a family of proteins that also includes the lipoma preferred partner (LPP) and thyroid receptor-interacting protein 6 (TRIP6). These zyxin family members display patterns of expression that significantly overlap that of zyxin. Western blot analysis indicates that there is no detectable upregulation of either LPP or TRIP6 expression in tissues derived from zyxin-null mice. Because zyxin family members may have overlapping functions, a comprehensive understanding of the role of these proteins in the mouse will require the generation of compound mutations in which multiple zyxin family members are simultaneously compromised.
authors.affiliation: Huntsman Cancer Institute and Department of Biology, University of Utah, Salt Lake City 84112, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Hoffman
authors.forename: David A
authors.initials: DA
authors.lastname: Nix
authors.forename: Beverly
authors.initials: B
authors.lastname: Benson
authors.forename: Ray
authors.initials: R
authors.lastname: Boot-Hanford
authors.forename: Erika
authors.initials: E
authors.lastname: Gustafsson
authors.forename: Colin
authors.initials: C
authors.lastname: Jamora
authors.forename: A Sheila
authors.initials: AS
authors.lastname: Menzies
authors.forename: Keow Lin
authors.initials: KL
authors.lastname: Goh
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Jensen
authors.forename: Frank B
authors.initials: FB
authors.lastname: Gertler
authors.forename: Elaine
authors.initials: E
authors.lastname: Fuchs
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001921:Brain / Q000254:growth & development*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000502:physiology* / Q000648:ultrastructure; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D060588:LIM Domain Proteins; D008168:Lung / Q000502:physiology; D008667:Metalloproteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D012098:Reproduction / Q000235:genetics; D013154:Spleen / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D016335:Zinc Fingers; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D060588:LIM Domain Proteins; C491227:Lpp protein, mouse; D008667:Metalloproteins; D008840:Microfilament Proteins; C092282:PSMC5 protein, human; D010750:Phosphoproteins; D014157:Transcription Factors; C498285:Zyx protein, mouse; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities