title: Expressional difference, distributions of TGF-β1 in TGF-β1 knock down transgenic mouse, and its possible roles in injured spinal cord.
abstract: Transforming growth factor β1 (TGF-β1) is a multi-functional cytokine implicated in many aspects of mammalian wound healing and scar tissue formation. However, few experiments have so far addressed the potential biological effects of TGF-β1 in the nervous system after injury, in addition to the immune system. In the present study, expressional silencing TGF-β1 was achieved by selecting predesigning hairpins targeting mouse TGF-β1 genes. Four homozygous transgenic offspring were generated and designed as Founder 90, Founder 12, Founder 41 and Founder 46. The down-regulated rates of TGF-β1 in different transgenic mice were also determined. To investigate the potential roles of TGF-β1, we observed changes in the neurological behavior of TGF-β1-knockdown (TGF-β1-kd) mice after spinal cord transection (SCT). Moreover, mRNA levels of inflammatory cytokines, including IL-1, IL-6, IL-10, NF-κB and TNF, were also detected in nucleate cells from blood by real-time PCR. Consequently, different TGF-β1 expressions were detected in multiple tissues, and protein levels of TGF-β1 decreased at different rates relative to that of wild type (WT) ones. The levels of TGF-β1 proteins in TGF-β1-kd mice decreased at most by 57% in Founder 90, which showed a significant recovery in Basso, Beattie, Bresnahan (BBB) scores after SCT compared with that of WT. However, expressions of immune relative genes showed no dramatic difference compared with WT ones. This study is the first to generate TGF-β1 down regulated mice and determine the possible roles of TGF-β1 in vivo in different conditions.
authors.affiliation: Institute of Neuroscience, Kunming Medical University, Kunming 650500, China.
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Xiyang
authors.forename: Bing-Tuan
authors.initials: BT
authors.lastname: Lu
authors.lastname: Ya-Zhao
authors.lastname: Yuan-Zhang
authors.forename: Qin-Jie
authors.initials: QJ
authors.lastname: Xia
authors.forename: Yu
authors.initials: Y
authors.lastname: Zou
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xiong-Zhi
authors.initials: XZ
authors.lastname: Quan
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Zhang
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000818:Animals; D005838:Genotype; D007249:Inflammation / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D013116:Spinal Cord / Q000378:metabolism* / Q000601:surgery; D013119:Spinal Cord Injuries / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
chemical_list: C556062:IL10 protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C577686:interleukin-6, mouse; D016753:Interleukin-10
keywords: TGF-β1; distribution and localization; knockdown; phenotype; protein expression; transgenic mouse