Print Email Facebook Twitter Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene Title Species specificity of human interleukin-3 demonstrated by cloning and expression of the homologous rhesus monkey (Macaca mulatta) gene Author Burger, H. van Leen, R.W. Dorssers, L.C.J. Persoon, N.L.M. Lemson, P.J. Wagemaker, G. Instituut voor Toegepaste Radiobiologie en Immunologie TNO Publication year 1990 Abstract To enable preclinical studies on homologous interleukin-3 (IL-3) in primate species, we isolated the gene encoding Rhesus monkey IL-3 (RhIL-3). The nucleotide sequence of the RhIL-3 gene displayed 92.9% homology with that of the human IL-3 (hIL-3) gene. The isolated RhIL-3 gene encodes a 143-amino acid (aa) precursor polypeptide, nine C-terminal residues shorter than the human protein. Protein homology was found to be 89.5% for the signal peptide (19 aa) and 80.5% for the mature protein (124 aa). Comparison of the human and RhIL-3 coding sequences showed that the majority of substitutions had occurred at amino acid replacement sites indicating a rapid evolution of the IL-3 protein. After expression of a genomic fragment in COS cells, RhIL-3 cDNA was constructed, which enabled large-scale production of the RhIL-3 polypeptide. RhIL-3 produced by Bacillus licheniformis and purified to homogeneity appeared to be approximately 100-fold more effective in stimulating Rhesus monkey hematopoietic progenitors than hIL-3, whereas RhIL-3 and hIL-3 showed comparable stimulatory activity on normal as well as malignant human hematopoietic cells. Thus, the rapid evolution of hIL-3 has resulted in a unidirectional species specificity, which most likely restricts the in vivo effects of hIL-3 in Macaca species. Subject Amino Acid SequenceAnimalBacillusBase SequenceCell LineCloning, MolecularComparative StudyDNAExonsGene ExpressionHematopoietic Stem CellsHumanInterleukin-3IntronsMacaca mulattaMolecular Sequence DataSequence Homology, Nucleic AcidSpecies SpecificityTransfection To reference this document use: http://resolver.tudelft.nl/uuid:9731cba0-421e-4429-ae8e-f5a8723ac548 TNO identifier 231098 ISSN 0006-4971 Source Blood, 76 (11), 2229-2234 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.