Potter M, Mushinski E B, Wax J S, Hartley J, Mock B A
Laboratory of Genetics, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Cancer Res. 1994 Feb 15;54(4):969-75.
BALB/cAn mice are highly susceptible to the induction of plasmacytomas (PCTs) by the i.p. injection of paraffin oils, whereas DBA/2 mice are solidly resistant. To search for genes that control the dominant resistant phenotype of DBA/2, BALB/c.DBA/2 (C.D2) congenic strains were constructed, and the susceptibility and resistance to PCT development were determined. PCT formation takes place over an extended period of 365 days but begins morphologically in focal proliferations of atypical plasma cells (foci) in the reactive oil granuloma that forms on mesenteric surfaces. Cells from some of these foci spread to other locations in oil granuloma tissue, forming new foci. Mice that develop six or more foci appear to be progressing towards eventual overgrowth and replacement of all peritoneal tissues with PCT cells. From Days 100 to 250, between 28 and 56% of PCT-susceptible BALB/cAn mice had 6 or more foci, whereas less than 5% of resistant DBA/2, BALB/c x DBA/2 F1 (hereafter called CD2F1), C57BL/6, and BALB/cJ mice had 6 or more foci. Four CD2 congenic strains carrying D2 alleles of genes on chromosomes other than chromosome 4 were highly susceptible. Between 0 and 20% of the mice in C.D2-Chr 4 congenic strains C.D2-MIA, C.D2-TF3, C.D2-Fv-1n/n, C.D2-Pnd7, C.D2-Lgm-1A, C.D2-Lgm-1B, C.D2-Lgm-1C, and C.D2-Lgm-1H developed 6 or more foci from 125 to 260 days, indicating resistance. The segments of DBA/2 chromosome 4 chromatin in C.D2-Fv-1n/n and C.D2-Pnd7 were discontinuous with those in C.D2-TF3, C.D2-Lgm-1A, C.D2-Lgm-1B, C.D2-Lgm-1C, and C.D2-Lgm-1H, indicating there are at least two genes (Pctr1 and Pctr2) in the distal half of this chromosome that confer resistance. Pctr1 is located between Ifa and D4Rck41, and Pctr2 is between Tnfr-1 and Pkcz. Each locus acting alone distinctly conferred a partial resistant phenotype. Pctr1 and Pctr2 did not appear to prevent the formation of clonal foci but did appear to limit the ability of the plasma cells in foci to acquire greater autonomy; thus, these genes affect tumor progression.
通过腹腔注射石蜡油，BALB/cAn小鼠极易诱发浆细胞瘤（PCT），而DBA/2小鼠则具有很强的抗性。为了寻找控制DBA/2显性抗性表型的基因，构建了BALB/c.DBA/2（C.D2）同源品系，并测定了其对PCT发生的易感性和抗性。PCT的形成持续365天，但在肠系膜表面形成的反应性油肉芽肿中，非典型浆细胞的局灶性增殖（病灶）在形态上首先出现。这些病灶中的一些细胞扩散到油肉芽肿组织的其他部位，形成新的病灶。出现6个或更多病灶的小鼠似乎正朝着最终过度生长并被PCT细胞取代所有腹膜组织的方向发展。在第100至250天期间，28%至56%的PCT易感BALB/cAn小鼠有6个或更多病灶，而抗性DBA/2、BALB/c×DBA/2 F1（以下称为CD2F1）、C57BL/6和BALB/cJ小鼠中只有不到5%有6个或更多病灶。携带4号染色体以外染色体上D2基因等位基因的4个CD2同源品系高度易感。在C.D2-Chr 4同源品系C.D2-MIA、C.D2-TF3、C.D2-Fv-1n/n、C.D2-Pnd7、C.D2-Lgm-1A、C.D2-Lgm-1B、C.D2-Lgm-1C和C.D2-Lgm-1H中，0%至20%的小鼠在125至260天内出现6个或更多病灶，表明具有抗性。C.D2-Fv-1n/n和C.D2-Pnd7中DBA/2 4号染色体染色质片段与C.D2-TF3、C.D2-Lgm-1A、C.D2-Lgm-1B、C.D2-Lgm-1C和C.D2-Lgm-1H中的不连续，表明该染色体远端一半至少有两个基因（Pctr1和Pctr2）赋予抗性。Pctr1位于Ifa和D4Rck41之间，Pctr2位于Tnfr-1和Pkcz之间。每个位点单独作用明显赋予部分抗性表型。Pctr1和Pctr2似乎并没有阻止克隆病灶的形成，但似乎确实限制了病灶中浆细胞获得更大自主性的能力；因此，这些基因影响肿瘤进展。
