Systemic Loss of C-terminal Src Kinase Expression Elicits Spontaneous Suppurative Inflammation in Conditional Knockout Mice

C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src family of kinases. The Src family of kinases are nonreceptor tyrosine kinases that regulate inflammation, cell proliferation, motility, and adhesion. To investigate potential histologic lesions associated with systemic...

Full description

Saved in:
Bibliographic Details
Published in:Veterinary pathology 2018-03, Vol.55 (2), p.331-340
Main Authors: Berman-Booty, Lisa D., Eraslan, Rukiye, Hanumegowda, Umesh, Cantor, Glenn H., Bounous, Denise I., Janovitz, Evan B., Jones, Beverly K., Buiakova, Olesia, Hayward, Michael, Wee, Susan
Format: Article
Language:English
Subjects:
Animals
Blotting, Southern
Female
Gene Expression
Inflammation - metabolism
Inflammation - pathology
Inflammation - veterinary
Male
Mice, Knockout - metabolism
src-Family Kinases - metabolism
Suppuration - metabolism
Suppuration - pathology
Suppuration - veterinary
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src family of kinases. The Src family of kinases are nonreceptor tyrosine kinases that regulate inflammation, cell proliferation, motility, and adhesion. To investigate potential histologic lesions associated with systemic loss of Csk gene activity in adult mice, conditional Csk-knockout mice were examined. Cre-mediated systemic excision of Csk induced by tamoxifen treatment resulted in multiorgan inflammation. Specifically, induction of Csk gene excision with three days of tamoxifen treatment resulted in greater than 90% gene excision. Strikingly, these mice developed enteritis that ranged from minimal and suppurative to severe, fibrinonecrosuppurative and hemorrhagic. Other inflammatory lesions included suppurative pneumonia, gastritis, and myocarditis, and increased numbers of inflammatory cells within the hepatic parenchyma. When tamoxifen treatment was reduced from three days to one day in an effort to lower the level of Csk gene excision and limit lesion development, the mice developed severe suppurative to pyogranulomatous pneumonia and minimal to mild suppurative enteritis. Lesions observed secondary to Csk gene excision suggest important roles for Csk in downregulating the proinflammatory activity of the Src family of kinases and limiting neutrophil-mediated inflammation.
ISSN:0300-9858
1544-2217
DOI:10.1177/0300985817747330