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DOI: 10.1055/s-0037-1615616
Targeted Disruption of the Mouse Gz-alpha Gene: A Role for Gz in Platelet Function?
Publikationsverlauf
Received
25. April 2000
Accepted after resubmission
28. September 2000
Publikationsdatum:
08. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200103/lookinside/thumbnails/10-1055-s-0037-1615616-1.jpg)
Summary
Gz is one of nine G proteins identified in platelets and its role in these cells is unknown. Our laboratory has generated a mouse deficient in the Gz-alpha gene in the hope of determining its in vivo function. Bleeding times from the tail tip of Gzα deficient mice was significantly longer than wild type mice. Platelet aggregation and ATP secretion did not differ between wild type and Gzα deficient mice. When mice were presented with a thromboembolism challenge no differences were observed in the survival or mortality of wild type or Gzα deficient mice, however a strain difference was observed. Ignoring the genetic background of a mutant mouse might lead to a misinterpretation of results and thus it is absolutely critical to take the genetic background into account when assessing any aspect of a mutant mouse.
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References
- 1 Brass LF, Hoxie JA, Manning DR. Signaling through G proteins and G protein-coupled receptors during platelet activation. Thromb Haemost 1993; 70: 217-23.
- 2 Matsuoka M, Itoh H, Kozasa T, Kaziro Y. Sequence analysis of cDNA and genomic DNA for a putative pertussis toxin-insensitive guanine nucleotide-binding regulatory protein alpha subunit. Proc Natl Acad Sci USA 1988; 85: 5384-8.
- 3 Fong HK, Yoshimoto KK, Eversole-Cire P, Simon MI. Identification of a GTP-binding protein alpha subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc. Natl. Acad. Sci. USA 1988; 85: 3066-70.
- 4 Fields TA, and Casey PJ. Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins. Biochem. J 1997; 321: 561-71.
- 5 Offermanns S, Toombs CF, Hu YH, Simon MI. Defective platelet activation in G alpha(q)-deficient mice. Nature 1997; 389: 183-6.
- 6 Simonds WF. G protein regulation of adenylate cyclase. Trends Pharmacol. Sci. 1999; 20: 66-73.
- 7 Klages B, Brandt U, Simon MI, Schultz G, Offermanns S. Activation of G12/G13 results in shape change and Rho/Rho-kinase- mediated myosin light chain phosphorylation in mouse platelets. J Cell. Biol. 1999; 144: 745-54.
- 8 Ledermann B, and Burki K. Establishment of a germ-line competent C57BL/6 embryonic stem cell line. Exp. Cell. Res. 1991; 197: 254-8.
- 9 Thomas KR, and Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 1987; 51: 503-12.
- 10 Mansour SL, Thomas KR, Capecchi MR. Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 1988; 336: 348-52.
- 11 Nitschke L, Kopf M, Lamers MC. Quick nested PCR screening of ES cell clones for gene targeting events. Biotechniques 1993; 14: 914-6.
- 12 DiMinno G, and Silver MJ. Mouse antithrombotic assay: a simple method for the evaluation of antithrombotic agents in vivo. Potentiation of anti-thrombotic activity by ethyl alcohol. J Pharmacol Exp Ther 1983; 225: 57-60.
- 13 Rosenblum WI, Nelson GH, Cockrell CS, Ellis EF. Some properties of mouse platelets. Thromb. Res. 1983; 30: 347-55.
- 14 Brusa R. Genetically modified mice in neuropharmacology. Pharmacol. Res. 1999; 39: 405-19.
- 15 Matsusaka T, Fogo A, Ichikawa I. Targeting the genes of angiotensin receptors. Semin. Nephrol. 1997; 17: 396-403.
- 16 Blendy JA, Kaestner KH, Schmid W, Gass P, Schutz G. Targeting of the CREB gene leads to up-regulation of a novel CREB mRNA isoform. EMBO J 1996; 15: 1098-106.
- 17 Faraci FM, and Sigmund CD. Vascular biology in genetically altered mice. Smaller vessels, bigger insight. Circ. Res. 1999; 85: 1214-25.
- 18 Ui M. Islet-activating protein, pertussis toxin: a probe for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase. Trends Pharmacol Sci 1984; 5: 277-9.
- 19 Lapetina EG, Reep B, Chang KJ. Treatment of human platelets with trypsin, thrombin, or collagen inhibits the pertussis toxin-induced ADPribosylation of a 41-kDa protein. Proc. Natl. Acad. Sci. USA 1986; 83: 5880-3.
- 20 Mutant mice and neuroscience: recommendations concerning genetic background.. Banbury Conference on genetic background in mice. Neuron 1997; 19: 755-9.