Micronuclei, whole or fragmented chromosomes spatially separated from the main nucleus, are associated with genomic instability and have been identified as drivers of tumorigenesis. Paradoxically, Kif18a mutant mice produce micronuclei due to asynchronous segregation of unaligned chromosomes in vivo but do not develop spontaneous tumors. We report here that micronuclei in Kif18a mutant mice form stable nuclear envelopes. Challenging Kif18a mutant mice via deletion of the Trp53 gene led to formation of thymic lymphoma with elevated levels of micronuclei. However, loss of Kif18a had modest or no effect on survival of Trp53 homozygotes and heterozygotes, respectively. Micronuclei in cultured KIF18A KO cells form stable nuclear envelopes characterized by increased recruitment of nuclear envelope components and successful expansion of decondensing chromatin compared with those induced by nocodazole washout or radiation. Lagging chromosomes were also positioned closer to the main chromatin masses in KIF18A KO cells. These data suggest that not all micronuclei actively promote tumorigenesis.

中文翻译：

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Kif18a突变小鼠的微核形成稳定的微核包膜并且不会促进肿瘤发生

微核，即与主核在空间上分离的完整或片段染色体，与基因组不稳定相关，并已被确定为肿瘤发生的驱动因素。矛盾的是，Kif18a 突变小鼠由于体内未对齐染色体的异步分离而产生微核，但不会产生自发性肿瘤。我们在这里报道 Kif18a 突变小鼠的微核形成稳定的核膜。通过删除 Trp53 基因来攻击 Kif18a 突变小鼠，会导致胸腺淋巴瘤的形成，且微核水平升高。然而，Kif18a 的缺失分别对 Trp53 纯合子和杂合子的存活影响不大或没有影响。培养的 KIF18A KO 细胞中的微核形成稳定的核膜，其特征是与诺考达唑冲洗或辐射诱导的微核相比，核膜成分的募集增加和解浓缩染色质的成功扩增。KIF18A KO 细胞中滞后染色体的位置也更靠近主要染色质团。这些数据表明并非所有微核都会积极促进肿瘤发生。