Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.
NanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznan, Poland.
Int J Mol Sci. 2022 Apr 29;23(9):4932. doi: 10.3390/ijms23094932.
The B-cell CLL/lymphoma 11B gene (BCL11B) plays a crucial role in T-cell development, but its role in T-cell malignancies is still unclear. To study its role in the development of T-cell neoplasms, we generated an inducible BCL11B knockout in a murine T cell leukemia/lymphoma model. Mice, bearing human oncogenes TAL BHLH Transcription Factor 1 (TAL1; SCL) or LIM Domain Only 1 (LMO1), responsible for T-cell acute lymphoblastic leukemia (T-ALL) development, were crossed with BCL11B floxed and with CRE-ER/lox mice. The mice with a single oncogene BCL11Bflox/floxCREtg/tgTAL1tg or BCL11Bflox/floxCREtg/tgLMO1tg were healthy, bred normally, and were used to maintain the mice in culture. When crossed with each other, >90% of the double transgenic mice BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg, within 3 to 6 months after birth, spontaneously developed T-cell leukemia/lymphoma. Upon administration of synthetic estrogen (tamoxifen), which binds to the estrogen receptor and activates the Cre recombinase, the BCL11B gene was knocked out by excision of its fourth exon from the genome. The mouse model of inducible BCL11B knockout we generated can be used to study the role of this gene in cancer development and the potential therapeutic effect of BCL11B inhibition in T-cell leukemia and lymphoma.
B 细胞慢性淋巴细胞白血病/淋巴瘤 11B 基因（BCL11B）在 T 细胞发育中发挥着关键作用，但它在 T 细胞恶性肿瘤中的作用尚不清楚。为了研究其在 T 细胞肿瘤发生中的作用，我们在小鼠 T 细胞白血病/淋巴瘤模型中生成了一种可诱导的 BCL11B 敲除。携带人类癌基因 TAL 碱性亮氨酸拉链转录因子 1（TAL1；SCL）或 LIM 结构域仅 1（LMO1）的小鼠，负责 T 细胞急性淋巴细胞白血病（T-ALL）的发展，与 BCL11B 基因敲除和 CRE-ER/lox 小鼠交配。具有单个癌基因 BCL11Bflox/floxCREtg/tgTAL1tg 或 BCL11Bflox/floxCREtg/tgLMO1tg 的小鼠健康，正常繁殖，并用于维持培养中的小鼠。当彼此交配时，超过 90%的双转基因小鼠 BCL11Bflox/floxCREtg/tgTAL1tgLMO1tg 在出生后 3 至 6 个月内自发发展为 T 细胞白血病/淋巴瘤。给予合成雌激素（他莫昔芬），它与雌激素受体结合并激活 Cre 重组酶，可从基因组中切除 BCL11B 基因的第四个外显子，从而敲除 BCL11B 基因。我们生成的可诱导 BCL11B 敲除小鼠模型可用于研究该基因在癌症发展中的作用以及 BCL11B 抑制在 T 细胞白血病和淋巴瘤中的潜在治疗效果。
