A gain-of-function filamin A mutation in mouse platelets induces thrombus instability

January 1, 2023
J Thromb Haemost
https://pubmed.ncbi.nlm.nih.gov/36006037

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/36006037

Research summary

This study investigates the impact of a gain-of-function mutation in filamin A (FLNA) on platelet function and thrombus stability. Using a conditional Knockin mouse model expressing a mutant FLNA specifically in megakaryocytes and platelets, researchers observed enhanced platelet aggregation and activation. However, in vivo experiments revealed increased thrombus instability, characterized by frequent embolization, suggesting that the mutation leads to hyperactive but unstable thrombi.

Key outcome of the study

The gain-of-function FLNA mutation enhances platelet activation and aggregation but compromises thrombus stability in vivo, leading to increased embolization. This highlights the critical role of FLNA in maintaining thrombus integrity and suggests that certain FLNA mutations may predispose individuals to thrombotic disorders.

Mouse model

Flna conditional Knockin mouse model developed by genOway, featuring a loxP-flanked wild-type exon 45 of the Flna gene replaced by a mutant exon 45 harboring a human C-terminal frameshift mutation. The mutation is specifically expressed in the megakaryocyte/platelet lineage using the PF4-Cre system.

TARGET:
Flna
Filamin A, ABP-280

Keywords

Thrombosis, Platelet function, Filamin A, Hemostasis, Thrombus stability

Technical specifications

Conditional Knockin model, PF4-Cre driver, LoxP-flanked exon replacement, Humanized mutation, Megakaryocyte-specific expression

Related products

Catalogue product

No items found.

Customized product

Humanized KI mouse

Use humanized mice as in vivo tools for mimicking human pathological conditions and diseases, and for conducting preclinical research.

Tissue-specific KO mouse

Use tissue- or cell-specific conditional Knockout mouse models to bypass embryonic lethality, compensatory mechanisms, complex phenotypes, etc.