Interleukin-3 (IL-3) poor-responsive inbred mouse strains carry the identical deletion of a branch point in the IL-3 receptor alpha subunit gene.
Interleukin-3 (IL-3) stimulates colony formation of multiple lineages of hematopoietic cells. Bone marrow cells of A/J mice are nonresponsive to IL-3, and this observation has recently been correlated with aberrant mRNA splicing and impaired expression of the IL-3 receptor alpha subunit (IL-3R alpha), a binding component of the high-affinity receptors. We examined the IL-3R alpha gene in 27 inbred mouse strains and found the identical mutation, a 5-bp deletion at the branch point of intron 7, in 10 of these mouse strains. Bone marrow cells isolated from these 10 mouse strains did not express IL-3R alpha on the cell surface and did not form colonies in response to IL-3. Because the defective IL-3R alpha gene was found in several distantly related mouse strains, it appears to be a recessive allele rather than a sporadic mutation. In contrast, only 1 of 21 wild-derived mouse strains carried the 5-bp deletion in the IL-3R alpha gene. This study suggests that IL-3 function is not required for normal hematopoiesis in mice, but the retention of the IL-3 and IL-3R system may be of some selective advantage in wild populations.
Hara
T
T
Department of Cell Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
Ichihara
M
M
Takagi
M
M
Miyajima
A
A
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D003114:Colony-Forming Units Assay; D004252:DNA Mutational Analysis; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005796:Genes; D005808:Genes, Recessive; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D016185:Receptors, Interleukin-3 / Q000172:deficiency* / Q000235:genetics; D017384:Sequence Deletion
D007377:Interleukin-3; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3