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| Effects of CTRP6 Gene Deficiency on Mice (Mus musculus) Health |
| JI Miao1, 2, *, WU Wen-Jing2, *, ZHENG Cheng1, 2, XU Ke1, 2, HUANG Xin1, 2, PENG Yong-Jia2, TENG Yi-Qun3, ZHANG Jin2, **, DONGFANG Yang1, ** |
1 College of Agronomy and Biotechnology, Hebei Normal University of Science & Technology, Qinhuangdao 066000, China;
2 College of Biological Chemical Sciences and Engineering, Jiaxing University, Jiaxing 314000, China;
3 Jiaxing Second Hospital, Jiaxing 314000, China |
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Abstract C1q tumor necrosis factor-related protein 6 (CTRP6) differentially regulates the metabolism of porcine intramuscular and subcutaneous fat, thus it has potential value in high quality lean pig (Sus scrofa) breeding. However, the effect of CTRP6 deficiency on animal health is still unknown. CTRP6 knock-out (KO) mice (Mus musculus) was constructed, and litter size, body weight, food intake, behavioristics of stressful situations, tissue sections, related physiological markers and gene expression were analyzed. The purpose is to explicit effects of CTRP6 deficiency on mice health. The results showed that average litter size was 5.4±0.3 in KO mice and 5.7±0.7 in wild-type (WT) mice. The survival rate was (92.1±3.2)% in KO mice and (93.1±4.5)% in WT mice. Two genotypes showed no significant difference. Weight analysis showed that the body weight of 8-week-old KO and WT mice were (25.08±0.34) and (28.34±1.06) g, respectively. The body weight of KO mice was significantly lower than that of WT mice (P<0.05), so does the weight of white adipose tissue (P<0.05). However, two genotypes showed no difference in average daily food intake. In tail suspension test and forced swimming test, the immobility time of KO mice was longer than that of WT mice, which indicates that KO mice were inclined to give up struggling under pressure conditions. In open field test, the number of crossing scores in KO mice was significantly less than in WT mice, which suggests that KO mice lack of interests in exploring a new environment. In sucrose preference test, no difference was observed between 2 genotypes in the sucrose preference. In morris water maze experiment, KO and WT mice exhibited similar learning ability in the first 5 days of place navigation test, but the frequency per min of passing through the plague position was less in KO mice than in WT mice on the 6th day of spatial probe test, which indicated the memory ability of KO mice was decreased. Further analysis of tissue section and inflammatory marker genes in brain were conducted and KO mice exhibited a higher level of inflammation than WT mice. The expression of memory related genes FBJ osteosarcoma oncogene (c-fos) in hippocampus was analyzed and it was down-regulated in KO mice. In conclusion, CTRP6 deficiency has no significant effect on mice litter size and food intake, but it reduces the body weight and adipose accumulation of mice. A negative impact on stress tolerance, interests of exploration and memory ability are detected, which may be related to the enhancement of brain inflammation. This study provides a certain theoretical basis for the further application of CTRP6 in high-quality lean pig breeding production. This study provides a theoretical basis for further revealing the function of ctrp6 gene.
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Received: 07 August 2019
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Corresponding Authors:
** Corresponding authors, zhangjin7688@163.com; yang_dongfang@hotmail.com
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| About author:: * The authors who contribute equally |
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1 邓锦波, 王桂敏, 赵善廷, 等. 2009. Reeler小鼠海马齿状回形态结构与组织化学研究[J]. 解剖学报, 40(4): 522-526.
(Deng J B, Wang G M, Zhao S, et al.2009. Morphological and histochemical study of hippocampal dentate gyrus in reeler mice[J]. Acta Anatomica Sinica, 40(4): 522-526.)
2 杜娜. 2015. 枳菊解郁汤对抑郁模型小鼠的抗抑郁作用及其神经机制[D]. 硕士学位论文, 曲阜师范学院, 导师: 李亚. pp. 1-60.
(Du N.2015. Antidepressant effect and neural mechanism of qiju jieyu decoction on depression model mice[D]. Thesis for M. S., Qufu Normal University, Supervisor: Li Y, pp. 1-60.)
3 黄万龙, 张秀秀, 李嫒, 等. 2017. 利用RNA-seq技术筛选大白猪皮下和肌内脂肪组织差异表达基因[J]. 遗传, 39(6): 501-511.
(Huang W L, Zhang X X, Li Y, et al.2017. Identification of differentially expressed genes between subcutaneous and intramuscular adipose tissue of Large White pig using RNA-seq[J]. Hereditas, 39(6): 501-511.)
4 孔唯力, 黄鑫, 徐珂, 等. 2018. CTRP6基因缺失对小鼠白色脂肪组织“棕色化”的影响[J]. 中国细胞生物学学报, 40(12): 52-61.
(Kong W L, Huang X, Xu K, et al.2018. Allele deficiency of CTRP6 affects the browning of white adipose tissue in mice[J]. Chinese Journal of Cell Biology, 40(12): 2018-2027.)
5 李爱萍, 赵慧, 李韶, 等. 2005. 不同鼠种在Morris水迷宫学习记忆行为中的种属差异[J]. 中国行为医学科学, 14(1): 29-31.
(Li A P, Zhao H, Li S, et al.2005. Species differences of muridae in the learning and memory behavior in morris water maze[J]. Chinese Journal of Behavioral Medical Science, 14(1): 29-31.)
6 梁如, 殷佳, 潘晔, 等. 2018. 交泰丸对慢性温和不可预知性应激抑郁模型大鼠炎性细胞因子的影响[J]. 中草药, 49(5): 1100-1105.
(Liang R, Yin J, Pan Y, et al.2018. Effects of jiaotai pill on inflammatory cytokines in depression model mice with chronic unpredictable mild stress[J]. Chinese Traditional and Herbal Drugs, 49(5): 1100-1105.)
7 刘海艳, 冯斌, 王济, 等. 2018. 天麻素对抑郁症模型小鼠抑郁行为及其相关细胞因子表达的影响[J]. 中南药学, 16(2): 166-170.
(Liu H Y, Feng B, Wang J, et al.2018. Effect of gastrodin on the depression-like behaviors and the expression of inflammatory factors in mice[J]. Central South Pharmacy, 16(2): 166-170.)
8 罗玲玲. 2019. 猪肉质量性状的育种策略[J]. 养殖与饲料, (07): 1-4.
(Luo L L. 2019. Breeding strategies for pork 1uality traits[J]. Animals Breeding and Feed, (07): 1-4.)
9 孙世光, 李自发, 孙鹏, 等. 2011. 昆明小鼠旷场实验评价方法的三维结构[J]. 中华行为医学与脑科学杂志, 20(10): 875-877.
(Sun S G, Li Z F, Sun P, et al.2011. Open field test as a method for ethology in kunming mice: Three behavioral dimensions by factor analysis[J]. Chinese Journal of Behavioral Medicine and Brain Science, 20(10): 875-877.)
10 毋文静. 2016. CTRP6调控猪脂肪细胞成脂的作用与机制[D]. 博士学位论文, 西北农林科技大学, 导师: 杨公社. pp. 1-113.
(Wu W J.2016. The function and mechanism of complement-C1q/TNF-related protein 6 during adipogenesis of porcine adipocytes[D]. Thesis for Ph.D., Northwest A＆F University, Supervisor: Yang G S. pp. 1-113.)
11 周瑞. 2015. Cathepsin D缺陷小鼠的行为学及其机制的研究[D]. 博士学位论文, 浙江大学, 导师: 段树民. pp. 1-103.
(Zhou R.2015. Behavioral phenotype of Cathepsin D-deficient mice[D]. Thesis for Ph.D., Zhejiang University, Supervisor: Duan S M, pp. 1-103.)
12 Barbeau E J, Chauvel P, Moulin C J A, et al.2017. Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms[J]. Hippocampus, 27(4): 405-416.
13 Can A, Dao D T, Arad M, et al.2012. The mouse forced swim test[J]. JoVE (Journal of Visualized Experiments), (59): e3638.
14 Can A, Dao D T, Terrillion C E, et al.2012. The tail suspension test[J]. JoVE (Journal of Visualized Experiments), (59): e3769.
15 Chen J, Shu S, Chen Y, et al.2019. AIM2 deletion promotes neuroplasticity and spatial memory of mice[J]. Brain Research Bulletin, 152: 85-94.
16 Cruz F C, Rubio F J, Hope B T.2015. Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction[J]. Brain Research, 1628: 157-173.
17 Lee M H, Kim H, Lim B V, et al.2003. Naloxone potentiates treadmill running-induced increase in c-Fos expression in rat hippocampus[J]. Life Sciences, 73(24): 3139-3147.
18 Lei X, Seldin M M, Little H C, et al.2017. C1q/TNF-related protein 6 (CTRP6) links obesity to adipose tissue inflammation and insulin resistance[J]. Journal of Biological Chemistry, 292(36): 14836-14850.
19 Niu H, Ding S, Li H, et al.2018. Effect of long-term sodium salicylate administration on learning, memory, and neurogenesis in the rat hippocampus[J]. BioMed Research International, 2018: 1-10.
20 Ren T, Liu J, Ge Y, et al.2019. Chronic oleoylethanolamide treatment attenuates diabetes-induced mice encephalopathy by triggering peroxisome proliferator-activated receptor alpha in the hippocampus[J]. Neurochemistry International, 129: 104501.
21 Sáenz J C B, Villagra O R, Trías J F.2006. Factor analysis of forced swimming test, sucrose preference test and open field test on enriched, social and isolated reared rats[J]. Behavioural Brain Research, 169(1): 57-65.
22 Schäffler A, Buechler C.2012. CTRP family: Linking immunity to metabolism[J]. Trends in Endocrinology & Metabolism, 23(4): 194-204.
23 Snyder J S, Soumier A, Brewer M, et al.2011. Adult hippocampal neurogenesis buffers stress responses and depressive behaviour[J]. Nature, 476(7361): 458.
24 Strekalova T, Spanagel R, Bartsch D, et al.2004. Stress-induced anhedonia in mice is associated with deficits in forced swimming and exploration[J]. Neuropsychopharmacology, 29(11): 2007.
25 Suzuki K, Irie M, Kadowaki H, et al.2005. Genetic parameter estimates of meat quality traits in Duroc pigs selected for average daily gain, longissimus muscle area, backfat thickness, and intramuscular fat content[J]. Journal of Animal Science, 83(9): 2058-2065.
26 Tomida S, Mamiya T, Sakamaki H, et al.2009. Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail suspension and forced swimming tests[J]. Nature Genetics, 41(6): 688.
27 Vorhees C V, Williams M T.2006. Morris water maze: Procedures for assessing spatial and related forms of learning and memory[J]. Nature Protocols, 1(2): 848.
28 Wong G W, Krawczyk S A, Kitidis-Mitrokostas C, et al.2008. Molecular, biochemical and functional characterizations of C1q/TNF family members: Adipose-tissue-selective expression patterns, regulation by PPAR-γ agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions[J]. Biochemical Journal, 416(2): 161-177.
29 Wong G W, Wang J, Hug C, et al.2004. A family of Acrp30/adiponectin structural and functional paralogs[J]. Proceedings of the National Academy of Sciences of the USA, 101(28): 10302-10307.
30 Wu W, Mo D, Zhao C, et al.2015. Knockdown of CTRP6 inhibits adipogenesis via lipogenic marker genes and Erk1/2 signalling pathway[J]. Cell Biology International, 39(5): 554-562.
31 Wu W, Zhang J, Zhao C, et al.2017. CTRP6 regulates porcine adipocyte proliferation and differentiation by the AdipoR1/MAPK signaling pathway[J]. Journal of Agricultural and Food Chemistry, 65(27): 5512-5522.
32 Wu W, Zhang J, Zhao C, et al.2018. Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice[J]. Experimental Cell Research, 367(1): 15-23.
33 Yoshikawa T, Watanabe A, Ishitsuka Y, et al.2002. Identification of multiple genetic loci linked to the propensity for 'behavioral despair' in mice[J]. Genome Research, 12(3): 357-366.
34 Yu J, Xu W, Luo Y, et al.2019. Dynamic monitoring of depressive behavior induced by nonylphenol and its effect on synaptic plasticity in rats[J]. Science of the Total Environment, 689: 1012-1022.
35 Zheng S, Liu C, Huang Y, et al.2017. Effects of 2, 2', 4, 4'-tetrabromodiphenyl ether on neurobehavior and memory change and bcl-2, c-fos, grin1b and lingo1b gene expression in male zebrafish (Danio rerio)[J]. Toxicology and Applied Pharmacology, 333: 10-16. |
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