Genetically modified mice are provided comprising a nucleic acid sequence encoding a human M-CSF protein. Also provided are genetically modified mice comprising a nucleic acid sequence encoding a human M-CSF protein that is engrafted with human cells such as human hematopoietic cells, and methods of making such engrafted mice. These mice are used in many applications, for example, modeling of human immune diseases and pathogen infections; For example, in vivo screening for agents that modulate hematopoietic cell development and/or activity in a healthy or diseased state; In vivo screening for drugs toxic to hematopoietic cells; In vivo screening for agents that prevent, mitigate, or reverse the toxic effect of toxic substances on hematopoietic cells; It finds use in in vivo screening of individual human hematopoietic cells, etc. for predicting individual responsiveness to disease treatment.
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