RESUMO
Interleukin-8 (IL-8), a member of the chemokine alpha subfamily, is a chemoattractant for neutrophils. Cell surface receptors for IL-8 have been cloned from rabbits and humans. Two related but different IL-8 receptors (IL-8R) have been characterized from humans. IL-8RA and IL-8RB bind IL-8 at high affinity but IL-8RB also binds GRO/MGSA and NAP-2 at high affinity. Using the human IL-8RB cDNA as a probe, we have determined that the homologous murine gene maps near the Ity-Lsh-Bcg disease resistance locus. A murine homologue of the human IL-8RB was isolated from a genomic library. This gene would encode a protein of 359 amino acids and would have a 68 and 71% amino acid identity with human IL-8RA and IL-8RB, respectively. Additional mapping data using the murine gene revealed the following genetic distances (in cM +/- 1 standard error) from the centromere: Mylf--7.9 +/- 2.7--Lsh-Ity-Bcg--1.9 +/- 1.4--Il8rb--1.9 +/- 1.4--Vil-- 5.9 +/- 2.3--Acrg--2.9 +/- 1.7--Bcl-2.
Assuntos
Receptores de Interleucina/genética , Receptores de Interleucina/isolamento & purificação , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , DNA , Humanos , Imunidade Inata/genética , Camundongos , Dados de Sequência Molecular , Receptores de Interleucina-8A , Receptores de Interleucina-8BRESUMO
Plasmacytomas (PCTs) were induced in 47% of BALB/cAnPt mice by the intraperitoneal injection of pristane, in 2% of (BALB/c x DBA/2N)F1, and in 11% of 773 BALB/cAnPt x (BALB/cAnPt x DBA/2N)F1 N2 backcross mice. This result indicates a multigenic mode of inheritance for PCT susceptibility. To locate genes controlling this complex genetic trait, tumor susceptibility in backcross progeny generated from BALB/c and DBA/2N (resistant) mice was correlated with alleles of 83 marker loci. The genotypes of the PCT-susceptible progeny displayed an excess homozygosity for BALB/c alleles within a 32-centimorgan stretch of mouse chromosome 4 (> 95% probability of linkage) with minimal recombination (12%) near Gt10. Another susceptibility gene on mouse chromosome 1 may be linked to Fcgr2 (90% probability of linkage); there were excess heterozygotes for Fcgr2 among the susceptible progeny and excess homozygotes among the resistant progeny. Regions of mouse chromosomes 4 and 1 that are correlated with PCT susceptibility share extensive linkage homology with regions of human chromosome 1 that have been associated with cytogenetic abnormalities in multiple myeloma and lymphoid, breast, and endocrine tumors.
