Cells of the mononuclear phagocytic lineage are essential for both innate and adaptive immunity. This strain is part of a two-gene approach to target monocytes and macrophages, but not conventional dendritic cells (cDCs). These transgenic mice carry a BAC encoding a diphtheria toxin receptor-mCherry fusion protein (DTR-mCherry) preceded by a loxP-flanked transcriptional Stop element under the control of the Csf1r promoter. Expression of cre recombinase excises the Stop element and allows transcription and translation of DTR-mCherry in cells expressing Csf1r. Animals expressing DTR-mCherry can be treated with diptheria toxin to selectively ablate these cell populations. Deletion of the floxed Stop element through crosses with Lyz2 (lysozyme 2)-cre mice (see Stock No. <a href="https://www.jax.org/strain/004781">004781</a>) leads to expression of DTR-mCherry in splenic monocytes but not cDCs of compound mutant mice. Ly6ChighCD115+ spleen monocytes uniformly express mCherry, whereas MHCIIhighCD11chigh cDCs do not. Single injections of diptheria toxin in these animals (4 ng/g body weight) result in a complete loss of peripheral blood and bone marrow monocytes after 24 hours. Peripheral blood Ly6Chigh monocytes return to normal levels after 3 days and are present in super-physiological levels in blood on days 4 and 5 before returning to baseline after day 6. &nbsp;

These transgenic mice carry a BAC encoding a diphtheria toxin receptor-mCherry fusion protein (DTR-mCherry) preceded by a loxP-flanked transcriptional Stop element under the control of the Csf1r promoter. They are part of a two-gene approach to target monocytes and macrophages, but not conventional dendritic cells (cDCs).

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