• TFR1, a membrane protein expressed across various cell and tissue types in the human body, plays a crucial role in facilitating iron transport and metabolism. TFR1 is markedly expressed in numerous types of cancer cells. Studies have demonstrated that targeting TFR1 can effectively suppress tumor growth and metastasis. Moreover, TFR1 is also implicated in other conditions such as anemia and neurodegenerative disorders, etc.
• Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor belonging to the immunoglobulin superfamily, primarily expressed in microglia in the brain and macrophages in the periphery. TREM2 is involved in various biological functions, including cell maturation, cell proliferation, cell survival, phagocytosis, and the regulation of inflammation. It serves as a central immune signaling hub that is induced by pathological conditions and plays a critical role in neurodegenerative diseases such as Alzheimer's disease as well as in cancer.
• Gene editing strategy:
• B-hTFR1/hTREM2 mice were obtained by mating B-hTFR1 mice (110861) and B-hTREM2 mice (111176). 
• Protein expression analysis:
• TFR1 was detected in heart, spleen, cortex and hippocampus from wild-type and homozygous B-hTFR1/hTREM2 mice. Human TREM2 was detected in spleen, cortex and hippocampus of homozygous B-hTFR1/hTREM2 mice, but not in wild-type mice.
• Application:
• This product is used for pharmacodynamics and safety evaluation of Alzheimer's disease (AD).

Gene targeting strategy for B-hTFR1/hTREM2 mice.

The exons 4-19 of mouse Tfr1 gene that encode extracellular domain are replaced by human counterparts in B-hTFR1/hTREM2 mice. The genomic region of mouse Tfr1 gene that encodes cytoplasmic portion is retained. The promoter, 5’UTR and 3’UTR region of the mouse gene are also retained. The chimeric TFR1 expression is driven by endogenous mouse Tfr1 promoter, while mouse Tfr1 gene transcription and translation will be disrupted.

The exons 1~5 and 3’UTR of mouse Trem2 gene that encode the full-length protein were replaced by human TREM2 exons 1~5 and 3’UTR in B-hTFR1/hTREM2 mice.

Western blot analysis of TFR1 and TREM2 protein expression in homozygous B-hTFR1/hTREM2 mice. Various tissue lysates were collected from wild-type C57BL/6 mice (+/+) and homozygous B-hTFR1/hTREM2 mice (H/H), and then analyzed by western blot with species-specific anti-TREM2 antibody (CST, 91068S) and anti-TFR1 antibody (Abcam, ab214039). 50 μg total proteins were loaded for western blotting analysis. TFR1 was detected in heart, liver, spleen, cortex and hippocampus from wild-type mice and homozygous B-hTFR1/hTREM2 mice. Human TREM2 was detected in spleen, cortex and hippocampus of homozygous B-hTFR1/hTREM2 mice, but not in wild-type mice.