The Cxcr4^{CreER(T2)-IRES-eGFP} Knockin mouse model as a universal tool to study functions of hematopoietic stem cell (HSC)-derived cells

Werner Y, et al. Cxcr4 distinguishes HSC‑derived monocytes from microglia and reveals monocyte immune responses to experimental stroke. Nat Neurosci. 2020

The Cxcr4 Knockin mouse model was designed and generated by genOway for a group of researchers, led by Prof. Ralf Stumm, who recently published their work in Nature Neuroscience.

By taking advantage of the CreER(T2)-IRES-eGFP design, the authors could distinguish HSC‑derived monocytes from tissue-resident microglia and macrophages, and demonstrate that Cxcr4 promotes initial monocyte infiltration and subsequent territorial restriction of monocyte-derived macrophages to infarct tissue.

This model is a powerful tool to:

• Trace the lineage of HSC-derived cells such as monocytes and microglia, due to eGFP expression under the control of the Cxcr4 promoter
• Track monocyte fate and function in injured brain tissues (e.g., experimental stroke), due to the inducible expression of Cre upon tamoxifen induction

Figure: Immunofluorescences for GFP, Iba1 and Tmem119 reveals the presence of Cxcr4⁺ cells after stroke induction in coronal brain sections. Interestingly, Cxcr4 is expressed in infiltrating monocytes, but not in reactive microglia.