Abstract: Methods are disclosed for identifying activators and inhibitors of actions of interleukin-34 (IL-34) that are independent of the colony stimulating factor-1 (CSF-1) receptor (CSF-1R) and play a role in development, homeostasis and disease.

Abstract: Provided are mutant class III receptor tyrosine kinases (RTKIII) comprising a mutation at the amino acid residue corresponding to the conserved cysteine at residue 432 (C432) or 439 (C439) of a mouse colony-stimulating factor (1) receptor (CSF-IR) precursor having the amino acid sequence of SEQ ID NO: 1, where the mutation is a replacement of the cysteine with an amino acid having an uncharged polar R group. Also provided are mutant RTKIIIs comprising a tyrosine to phenylalanine mutation. Additionally provided are extracellular domains of the above-identified mutant RTKIIIs comprising cysteine to serine mutations. Further provided are stable cell lines of macrophages lacking a native CSF-IR. Also provided are isolated nucleic acids encoding any of the above-described mutant RTKIIIs or extracellular domains. Vectors comprising those nucleic acids are also provided. Additionally provided are methods of preparing the above-identified stable cell lines.