New York State Department of Health, Wadsworth Center, Albany, New York, USA.
Department of Environmental Health Sciences, School of Public Health, University at Albany, Rensselaer, New York, USA.
Cell Biochem Funct. 2022 Mar;40(2):150-162. doi: 10.1002/cbf.3684. Epub 2022 Jan 2.
Gene and protein expression of BTBR T Itpr3 /J (BTBR) mice with autistic-like behaviours were compared with the C57BL/6J strain, which is considered to have normal immunity and behaviour. Notch signalling pathway was constitutively activated in the immune system and liver of BTBR T Itpr3 /J (BTBR) mice. Notch ligand 4 (Dll4), Notch receptors (Notch1 Notch2 and Notch3) and recombination signal binding protein for immunoglobulin κ j region (RBPJ) were increased both at gene and protein levels in BTBR spleens and thymi. Notch downstream transcriptional factors, Tbx21, Gata3, Rorc and FoxP3 were increased in BTBR spleens, Gata3 and FoxP3 were increased in BTBR thymi and BTBR mice have a high blood CD4/CD8 T cell ratio. Reduced nucleotide excision repair ability in BTBR spleens was associated with increased 8-oxoguanine, Ogg1 inhibition, an enhanced level of apoptotic thymocytes and higher expression of GATA-3. Ogg1 inhibition and enhanced GATA-3 expression also were detected in BTBR brain. Notch signal promoted mitochondrial dynamics switching to enhanced fission with an increased number and mass of mitochondria in immune cells of BTBR mice, but not in livers and brains. Constitutive influences on mitochondria exist in this mouse model of autism spectrum disorder; similar outcomes from environmental exposures might occur perinatally in susceptible individuals to affect the development of autism.
BTBR T Itpr3 /J（BTBR）自闭症样行为小鼠与 C57BL/6J 品系（被认为具有正常免疫和行为的小鼠）的基因和蛋白表达进行了比较。BTBR T Itpr3 /J（BTBR）小鼠的免疫系统和肝脏中 Notch 信号通路持续激活。Notch 配体 4（Dll4）、Notch 受体（Notch1、Notch2 和 Notch3）和免疫球蛋白 κ j 区重组信号结合蛋白（RBPJ）在 BTBR 脾和胸腺中的基因和蛋白水平均增加。Notch 下游转录因子 Tbx21、Gata3、Rorc 和 FoxP3 在 BTBR 脾中增加，Gata3 和 FoxP3 在 BTBR 胸腺中增加，BTBR 小鼠血液中 CD4/CD8 T 细胞比例升高。BTBR 脾中核苷酸切除修复能力降低与 8-氧鸟嘌呤增加、Ogg1 抑制、凋亡胸腺细胞水平升高和 GATA-3 表达增加有关。BTBR 脑也检测到 Ogg1 抑制和增强的 GATA-3 表达。Notch 信号促进线粒体动力学向增强的分裂转变，导致 BTBR 小鼠免疫细胞中线粒体的数量和质量增加，但在肝脏和大脑中没有增加。这种自闭症谱系障碍小鼠模型存在对线粒体的固有影响；在易感个体中，围产期的环境暴露可能会产生类似的结果，从而影响自闭症的发展。
