Key Laboratory of Animal Resistance of Shandong Province, College of Life Science, Shandong Normal University, Jinan, 250000, P. R. China.
Department of Neurology, General Hospital of Jinan Military Command of PLA, Jinan, 250000, P. R. China.
Rev Cardiovasc Med. 2019 Sep 30;20(3):179-186. doi: 10.31083/j.rcm.2019.03.31813.
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathyis a rare form of inherited cerebral small vessel disease associated with mutations in the high-temperature requirement serine peptidase A1 gene. As of now, only about 50 cases have been reported. In 2012, our group reported a family with a novel mutant of the high-temperature requirement serine peptidase A1 gene in China for the first time. To further explore the molecular pathogenesis of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, a recombination mouse model expressed human high-temperature requirement serine peptidase A1 gene mutant identified by our group was generated using the Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 system and termed the Mut-high-temperature requirement serine peptidase A1 gene mouse model. Results show that Mut-high-temperature requirement serine peptidase A1 gene mice present similar pathological characteristics to patients with cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, suggesting that the Mut-high-temperature requirement serine peptidase A1 gene mouse model was generated successfully. Moreover, apoptosis was induced in mouse brain vascular smooth muscle cells derived from Mut-high-temperature requirement serine peptidase A1 gene mice. In summary, the cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy mouse model described in this study will be beneficial to demonstrate the pathological mechanism of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy and provide new therapeutic targets for clinical treatment.
脑常染色体隐性动脉病伴皮质下梗死和脑白质病变是一种罕见的遗传性脑小血管病，与高温需求丝氨酸肽酶 A1 基因突变有关。截至目前，大约只有 50 例病例报告。2012 年，我们小组在中国首次报道了一例携带高温需求丝氨酸肽酶 A1 基因突变的新病例。为了进一步探讨脑常染色体隐性动脉病伴皮质下梗死和脑白质病变的分子发病机制，我们使用 Donor & Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 系统生成了表达我们小组鉴定的人高温需求丝氨酸肽酶 A1 基因突变体的重组小鼠模型，并将其命名为 Mut-high-temperature requirement serine peptidase A1 基因小鼠模型。结果表明，Mut-high-temperature requirement serine peptidase A1 基因小鼠表现出与脑常染色体隐性动脉病伴皮质下梗死和脑白质病变患者相似的病理特征，提示成功生成了 Mut-high-temperature requirement serine peptidase A1 基因小鼠模型。此外，Mut-high-temperature requirement serine peptidase A1 基因小鼠脑血管平滑肌细胞中诱导了细胞凋亡。综上所述，本研究中描述的脑常染色体隐性动脉病伴皮质下梗死和脑白质病变小鼠模型将有助于阐明脑常染色体隐性动脉病伴皮质下梗死和脑白质病变的病理机制，并为临床治疗提供新的治疗靶点。
