Beamer W G, Shultz K L, Tennent B J, Nadeau J H, Churchill G A, Eicher E M
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
Cancer Res. 1998 Aug 15;58(16):3694-9.
Spontaneous juvenile ovarian granulosa cell (GC) tumors that occur in young girls are similar to GC carcinomas that develop in SWR-derived inbred mice. We analyzed female offspring from a series of matings among SWR and SJL inbred mice for chromosomal loci underlying tumor susceptibility. Intercross F2 female mice were produced by reciprocal matings of (SWR x SJL)F1 and (SJL x SWR)F1 parents. Tumorigenesis in these F2 mice as well as in SWXJ recombinant inbred and congenic strains of mice derived from SWR and SJL showed significant (P < 0.001) association with Gct1, a dominant susceptibility locus on chromosome (CHR) 4 and with Gct2 on CHR 12. Suggestive (P < 0.01) association was found with Gct3 on CHR 15. A fourth susceptibility locus, Gct4 on CHR X, was demonstrated with a strong parent-of-origin effect associated with the paternal genotype. Imprinting and complex interactions among these four loci combine to establish the probability for GC tumorigenesis in this mouse model.
发生在年轻女孩身上的自发性青少年卵巢颗粒细胞瘤与源自SWR近交系小鼠的颗粒细胞癌相似。我们分析了SWR和SJL近交系小鼠一系列交配产生的雌性后代，以寻找肿瘤易感性的染色体位点。通过（SWR×SJL）F1和（SJL×SWR）F1亲本的相互交配产生杂交F2雌性小鼠。这些F2小鼠以及源自SWR和SJL的SWXJ重组近交系和同源系小鼠的肿瘤发生与4号染色体上的显性易感位点Gct1以及12号染色体上的Gct2有显著（P<0.001）关联。发现与15号染色体上的Gct3有提示性（P<0.01）关联。在X染色体上发现了第四个易感位点Gct4，它具有与父本基因型相关的强烈亲本效应。这四个位点之间的印记和复杂相互作用共同决定了该小鼠模型中颗粒细胞瘤发生的概率。
