Tyrobp-flox Mouse

TYROBP, also known as DAP12 or KARAP, is a transmembrane adaptor protein. It functions as a receptor-activating subunit in natural killer (NK) cells and is expressed in multiple cell types like monocytes, macrophages, dendritic cells, osteoclasts, and microglia. TYROBP acts as a downstream adaptor and signaling partner for several receptors, such as SIRP1β, CD33, CR3, and TREM2, which are involved in signal transduction, especially in maintaining brain homeostasis [1,2].

In Alzheimer's disease (AD) mouse models, TYROBP-deficient mice showed genetic resilience to amyloidosis and tauopathy. Learning and synaptic functions were preserved, and complement C1q accumulation was prevented [1]. In Huntington's disease (HD) Q175 mouse models, Tyrobp knockout decreased microglial expression of disease-associated genes, mitigated astrogliosis, and improved motor function [4]. In aortic dissection (AD) mouse models, global or myeloid cell-specific deficiency of Tyrobp increased AD incidence, while enhancement of Trem2/Tyrobp signaling protected against AD [3].

In conclusion, TYROBP is crucial for signal transduction across multiple receptors in various cell types. Studies using KO mouse models have revealed its significant roles in neurodegenerative diseases like Alzheimer's and Huntington's, as well as in cardiovascular conditions such as aortic dissection. These models help understand the gene's function in disease-related biological processes, providing potential therapeutic targets.