TPA KO And PAI-1-KO Mouse Models
Posted by Wendy Wise on
Innovative Research raises and supplies a variety of mouse models to use in research associated with Alzheimer’s Disease, obesity, stroke and brain damage, and aging. Of particular interest to these areas are our tPA KO and PAI-1-KO Mouse Models. Below we have selected a few scholarly findings to aid in your understanding of the research possibilities when using our mice to investigate illness and disease.
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Aging
The aim of this study is to investigate age-dependent decline of endogenous tPA and the effects of tPA decline on glymphatic function and cognitive outcome in mice.
Alzheimer's Disease
In Alzheimer’s disease, tPA is down regulated. Restoration of tPA activity, either by adding tPA or inhibiting PAI-1 can reduce the deposition of Amyloid-beta in Alzheimer’s disease, which is why our tPA KO mouse models work well for studying this disease.
tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β.
Park L, Zhou J, Koizumi K, Wang G, Anfray A, Ahn SJ, Seo J, Zhou P, Zhao L, Paul S, Anrather J, Iadecola C. J Neurosci. 2020 Oct 14;40(42):8160-8173.
Brain Damage & Stroke
The aim of the first study is to investigate age-dependent decline of endogenous tPA and the effects of tPA decline on glymphatic function and cognitive outcome in mice, while the second study investigates the impact of PAI-1 and PAI-2 on brain infarct volume using gene-deficient mice. Both our tPA KO and PAI-1 mice models are relevant to these studies.
tPA Deficiency in Mice Leads to Rearrangement in the Cerebrovascular Tree and Cerebroventricular Malformations. Stefanitsch C, Lawrence AL, Olverling A, Nilsson I, Fredriksson L. Front Cell Neurosci. 2015 Nov 30;9:456.
PAI-1 but Not PAI-2 Gene Deficiency Attenuates Ischemic Brain Injury After Experimental Stroke. Griemert EV, Recarte Pelz K, Engelhard K, Schäfer MK, Thal SC. Transl Stroke Res. 2019 Aug;10(4):372-380.
Obesity
In obese mice, like humans, there is reduced fibrinolysis and increased plasma PAI-1 and tPA, due largely to their increased hepatocyte expression. Fibrinolysis (dissolving of fibrin clots) is initiated by tissue-type plasminogen activator (tPA) and inhibited by plasminogen activator inhibitor 1 (PAI-1). In obese humans, plasma PAI-1 and tPA proteins are increased, but PAI-1 dominates, leading to reduced fibrinolysis and thrombosis. Both our tPA and PAI-1 Knock-In mouse models are effective for these types of studies.
Interacting hepatic PAI-1/tPA gene regulatory pathways influence impaired fibrinolysis severity in obesity. Zheng Z, Nakamura K, Gershbaum S, Wang X, Thomas S, Bessler M, Schrope B, Krikhely A, Liu RM, Ozcan L, López JA, Tabas I. J Clin Invest. 2020 Aug 3;130(8):4348-4359.