A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation and Blood Pressure Circadian Rhythm.
A Novel Diabetic Mouse Model for Real-Time Monitoring of Clock Gene Oscillation and Blood Pressure Circadian Rhythm.
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DOI：
10.1177/0748730418803719
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发表时间：
2019-03
影响因子：
3.5
通讯作者：
Gong MC
中科院分区：
文献类型：
--
作者：
Hou T;Su W;Guo Z;Gong MC
糖尿病患者血压 (BP) 昼夜节律紊乱的发生率较高，这与靶器官损伤和有害心血管事件的风险增加有关。由于缺乏能够实时监测时钟基因振荡的糖尿病动物模型，关于时钟基因在糖尿病血压昼夜节律破坏中的作用的信息有限。在这里，我们通过将 2 型糖尿病 db/db 小鼠与 mPer2Luc 敲入小鼠杂交，生成了一种新型糖尿病 db/db-mPer2Luc 小鼠模型。通过无线电遥测或代谢室获取血压、心率、运动活动以及食物和水摄入量的每日节律。 mPer2 生物发光的每日振荡由 LumiCycle 在组织外植体中实时记录，并由 IVIS 系统在体内记录。我们的结果表明 db/db-mPer2Luc 小鼠肥胖、糖尿病和葡萄糖不耐受。 db/db-mPer2Luc 小鼠表现出血压日节律受损，这与压力反射敏感性、运动活动和新陈代谢的日节律破坏有关，但与心率或食物和水摄入量无关。与对照小鼠相比，db/db-mPer2Luc 小鼠移植的外周组织中 mPer2 每日振荡的相位有不同程度的提前。相比之下，在移植的视交叉上核（SCN）中，mPer2 每日振荡没有检测到相移。此外，在 db/db-mPer2Luc 小鼠体内的肝脏、肾脏和颌下腺中也检测到了 mPer2 每日振荡的高级相移。总之，糖尿病 db/db-mPer2Luc 小鼠是一种新型动物模型，可以实时监测离体和体内 mPer2 昼夜节律。 db/db-mPer2Luc 小鼠的结果表明，外周组织中 mPer2 每日振荡的不同步导致糖尿病患者血压每日振荡的消失。
Diabetic patients have an increased prevalence of blood pressure (BP) circadian rhythm disruption, which is associated with increased risk of target organ damage and detrimental cardiovascular events. Limited information is available regarding the role of clock genes in the disruption of the BP circadian rhythm in diabetes due to the lack of a diabetic animal model that allows real-time monitoring of clock gene oscillation. Here, we generated a novel diabetic db/db-mPer2Luc mouse model by crossing the type 2 diabetic db/db mice with the mPer2Luc knock-in mice. The daily rhythms of BP, heart rate, locomotor activity, and food and water intake were acquired by radiotelemetry or metabolic chambers. The daily oscillation of mPer2 bioluminescence was recorded by LumiCycle in real-time in tissue explants and by IVIS system in vivo. Our results showed that the db/db-mPer2Luc mice were obese, diabetic and glucose intolerant. The db/db-mPer2Luc mice displayed a compromised BP daily rhythm, which was associated with the disruption of the daily rhythms in baroreflex sensitivity, locomotor activity, and metabolism, but not heart rate or food and water intake. The phase of the mPer2 daily oscillation was advanced to different extents in the explanted peripheral tissues from the db/db-mPer2Luc mice relative to that in the control mice. In contrast, no phase shift was detected in the mPer2 daily oscillation in the explanted suprachiasmatic nucleus (SCN). Moreover, the advanced phase shift of the mPer2 daily oscillation was also detected in the liver, kidney and submandibular gland in vivo in the db/db-mPer2Luc mice. In conclusion, the diabetic db/db-mPer2Luc mouse is a novel animal model that allows real-time monitoring of mPer2 circadian rhythms ex vivo and in vivo. The results from db/db-mPer2Luc mice suggest that the desynchrony of mPer2 daily oscillation in the peripheral tissues contributes to the loss of BP daily oscillation in diabetes.
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影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S
CLOCK 基因变异与 2 型糖尿病受试者中 2 型糖尿病和心血管疾病的发病率相关：PREDIMED 随机试验中的饮食调节。
影响因子：
9.3
作者：
Corella D;Asensio EM;Coltell O;Sorlí JV;Estruch R;Martínez-González MÁ;Salas-Salvadó J;Castañer O;Arós F;Lapetra J;Serra-Majem L;Gómez-Gracia E;Ortega-Azorín C;Fiol M;Espino JD;Díaz-López A;Fitó M;Ros E;Ordovás JM
通讯作者：
Ordovás JM
昼夜节律的代谢和能量学的融合。
DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bass J;Takahashi JS
通讯作者：
Takahashi JS
影响因子：
64.5
作者：
Chen, H;Charlat, O;Morgenstern, JP
通讯作者：
Morgenstern, JP
影响因子：
5.8
作者：
Caton, P. W.;Kieswich, J.;Sugden, M. C.
通讯作者：
Sugden, M. C.