M. Ichihara et al., IMPAIRED INTERLEUKIN-3 (IL-3) RESPONSE OF THE A J MOUSE IS CAUSED BY A BRANCH POINT DELETION IN THE IL-3 RECEPTOR-ALPHA SUBUNIT GENE/, EMBO journal, 14(5), 1995, pp. 939-950
Interleukin-3 (IL-3) alone does not support hematopoietic colony forma
tion of bone marrow cells from the A/J mouse. To elucidate the molecul
ar lesion in A/J mice, we examined expression of the alpha and beta su
bunits of the IL-3 receptor (IL-3R). While IL-3R beta was normally exp
ressed, IL-3R alpha was not detectable on the surface of A/J-derived c
ells by antibody staining. Genetic linkage analysis using recombinant
inbred mouse strains between A/J and IL-3-responsive C57BL/6 indicated
that the IL-3R alpha gene locus was responsible for the impaired IL-3
response in A/J mice. Molecular cloning and characterization of A/J-d
erived IL-3R alpha cDNA revealed that it lacked the sequence correspon
ding to exon 8, which encodes 10 amino acid residues in the extracellu
lar domain. The aberrant splicing was due to a 5 base pair deletion at
the branch point in intron 7 and was reproduced in heterologous cells
by transfecting with an IL-3R alpha minigene carrying the deleterious
intron. The A/J-specific abnormal form of IL-3R alpha was localized i
nside the cells, but not on the cell surface, providing the molecular
basis for the impaired IL-3 response in the A/J mouse.