Role of MEKK1 in Cell Survival and Activation of JNK and ERK Pathways Defined by Targeted Gene Disruption

1998 ◽  
Vol 282 (5395) ◽  
pp. 1911-1914 ◽  
Author(s):  
T. Yujiri
Keyword(s):  
Cell Survival ◽  
Gene Disruption ◽  
Targeted Gene Disruption

scholarly journals Generation and Analysis of Mice Lacking the Chemokine Fractalkine

2001 ◽  
Vol 21 (9) ◽  
pp. 3159-3165 ◽  
Author(s):  
Donald N. Cook ◽  
Shu-Cheng Chen ◽  
Lee M. Sullivan ◽  
Denise J. Manfra ◽  
Maria T. Wiekowski ◽  
...  
Keyword(s):  
Gene Disruption ◽  
Surface Marker ◽  
Wild Type ◽  
Blood Leukocytes ◽  
Targeted Gene Disruption ◽  
Behavioral Abnormalities ◽  
Inflammatory Stimuli ◽  
Membrane Bound ◽  
Deficient Mice

ABSTRACT Fractalkine (CX3CL1) is the first described chemokine that can exist either as a soluble protein or as a membrane-bound molecule. Both forms of fractalkine can mediate adhesion of cells expressing its receptor, CX3CR1. This activity, together with its expression on endothelial cells, suggests that fractalkine might mediate adhesion of leukocytes to the endothelium during inflammation. Fractalkine is also highly expressed in neurons, and its receptor, CX3CR1, is expressed on glial cells. To determine the biologic role of fractalkine, we used targeted gene disruption to generate fractalkine-deficient mice. These mice did not exhibit overt behavioral abnormalities, and histologic analysis of their brains did not reveal any gross changes compared to wild-type mice. In addition, these mice had normal hematologic profiles except for a decrease in the number of blood leukocytes expressing the cell surface marker F4/80. The cellular composition of their lymph nodes did not differ significantly from that of wild-type mice. Similarly, the responses offractalkine −/− mice to a variety of inflammatory stimuli were indistinguishable from those of wild-type mice.

scholarly journals Targeted Gene Disruption Reveals an Adhesin Indispensable for Pathogenicity of Blastomyces dermatitidis

1999 ◽  
Vol 189 (8) ◽  
pp. 1207-1216 ◽  
Author(s):  
T. Tristan Brandhorst ◽  
Marcel Wüthrich ◽  
Thomas Warner ◽  
Bruce Klein
Keyword(s):  
Gene Transfer ◽  
Gene Disruption ◽  
Reverse Genetics ◽  
Fungal Infections ◽  
Blastomyces Dermatitidis ◽  
Dimorphic Fungi ◽  
Targeted Gene Disruption ◽  
Allelic Replacement ◽  
Impaired Binding

Systemic fungal infections are becoming more common and difficult to treat, yet the pathogenesis of these infectious diseases remains poorly understood. In many cases, pathogenicity can be attributed to the ability of the fungi to adhere to target tissues, but the lack of tractable genetic systems has limited progress in understanding and interfering with the offending fungal products. In Blastomyces dermatitidis, the agent of blastomycosis, a respiratory and disseminated mycosis of people and animals worldwide, expression of the putative adhesin encoded by the WI-1 gene was investigated as a possible virulence factor. DNA-mediated gene transfer was used to disrupt the WI-1 locus by allelic replacement, resulting in impaired binding and entry of yeasts into macrophages, loss of adherence to lung tissue, and abolishment of virulence in mice; each of these properties was fully restored after reconstitution of WI-1 by means of gene transfer. These findings establish the pivotal role of WI-1 in adherence and virulence of B. dermatitidis yeasts. To our knowledge, they offer the first example of a genetically proven virulence determinant among systemic dimorphic fungi, and underscore the value of reverse genetics for studies of pathogenesis in these organisms.

scholarly journals Role of Group V Phospholipase A2in Zymosan-induced Eicosanoid Generation and Vascular Permeability Revealed by Targeted Gene Disruption

2004 ◽  
Vol 279 (16) ◽  
pp. 16488-16494 ◽  
Author(s):  
Yoshiyuki Satake ◽  
Bruno L. Diaz ◽  
Barbara Balestrieri ◽  
Bing K. Lam ◽  
Yoshihide Kanaoka ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Gene Disruption ◽  
Group V ◽  
Targeted Gene Disruption

scholarly journals Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption

2008 ◽  
Vol 105 (17) ◽  
pp. 6398-6402 ◽  
Author(s):  
P. Ellekvist ◽  
J. Maciel ◽  
G. Mlambo ◽  
C. H. Ricke ◽  
H. Colding ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Gene Disruption ◽  
Critical Role ◽  
K Channel ◽  
Targeted Gene Disruption

Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2599-2601 ◽  
Author(s):  
Eric O. Sekyere ◽  
Louise L. Dunn ◽  
Yohan Suryo Rahmanto ◽  
Des R. Richardson
Keyword(s):  
Metabolic Pathways ◽  
Gene Disruption ◽  
Vital Role ◽  
Plasminogen Activation ◽  
Serum Chemistry ◽  
Wild Type ◽  
Targeted Disruption ◽  
Targeted Gene Disruption

AbstractMelanotransferrin (MTf) or tumor antigen p97 is a transferrin homolog that binds one iron (Fe) atom and has been suggested to play roles in a variety of processes, including Fe metabolism, eosinophil differentiation, and plasminogen activation. Considering the vital role of Fe in many metabolic pathways, such as DNA and heme synthesis, it is important to understand the function of MTf. To define this, a MTf knockout (MTf–/–) mouse was generated through targeted disruption of the MTf gene. The MTf–/– mice were viable and fertile and developed normally, with no morphologic or histologic abnormalities. Assessment of Fe indices, tissue Fe levels, hematology, and serum chemistry parameters demonstrated no differences between MTf–/– and wild-type (MTf+/+) mice, suggesting MTf was not essential for Fe metabolism.

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