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遗传背景和性别对小鼠膀胱功能的影响。

Influence of genetic background and gender on bladder function in the mouse.

作者信息

Cornelissen Laura L, Misajet Blake, Brooks David P, Hicks Alexandra

机构信息

Urogenital Biology, Cardiovascular & Urogenital Centre of Excellence for Drug Discovery, GlaxoSmithKline Pharmaceuticals, Philadelphia, PA 19406, USA.

出版信息

Auton Neurosci. 2008 Jun;140(1-2):53-8. doi: 10.1016/j.autneu.2008.04.001. Epub 2008 May 20.

Abstract

Genetically targeted animals are used throughout research to investigate the role genes play in biological function, including the lower urinary tract. Generation of transgenic mice involves backcrossing for successive generations. Parental strain background genes can interact with the mutated gene potentially affecting interpretation of the mutant phenotype. Differences in physiological phenotypes may also be influenced by gender. The present study evaluated bladder function in five strains of male and female mice, 129S6/SvEvTac, A/J, B6129F1/Tac, BALB/cAnNCrL and C57BL/6NTacFBr. Urodynamic parameters were analyzed during infusion of saline (threshold and void volume, non-voiding contractions, pressure threshold and bladder contraction amplitude) in conscious mice and using voluntary urination in freely moving mice placed on filter paper (number of small and large diameter urine spots), which represent commonly used techniques in preclinical characterization of bladder function. Female BALB/c mice exhibited a significantly larger number of non-voiding contractions and urine dripping (increased number of small urine spots) compared to other female mice. Male BALB/c mice did not share this phenotype. Significant differences in threshold and void volumes were also noted amongst strains and genders. The numbers of large diameter urine spots differed amongst female, and not male, mouse strains. Gender differences were observed between sexes of the same strain in both large and small urine spots. These data demonstrate that genetic background and gender can influence bladder function in the mouse. These differences have a significant impact on the choice of strain and gender when investigating the effects of genetic manipulation on the micturition reflex.

摘要

在整个研究过程中,基因靶向动物被用于研究基因在生物功能中的作用,包括下尿路。转基因小鼠的培育涉及连续多代的回交。亲本品系背景基因可能与突变基因相互作用,从而潜在地影响对突变表型的解读。生理表型的差异也可能受性别影响。本研究评估了129S6/SvEvTac、A/J、B6129F1/Tac、BALB/cAnNCrL和C57BL/6NTacFBr这五个品系的雄性和雌性小鼠的膀胱功能。在清醒小鼠输注生理盐水期间(阈值和排尿量、非排尿收缩、压力阈值和膀胱收缩幅度)以及在置于滤纸上自由活动的小鼠进行自主排尿时(不同直径尿斑的数量)分析尿动力学参数,这些是膀胱功能临床前特征描述中常用的技术。与其他雌性小鼠相比,雌性BALB/c小鼠表现出显著更多的非排尿收缩和尿液滴漏(小尿斑数量增加)。雄性BALB/c小鼠没有这种表型。在品系和性别之间也注意到阈值和排尿量存在显著差异。不同雌性小鼠品系的大直径尿斑数量不同,而雄性小鼠品系间没有差异。在同一品系的雌雄小鼠中,无论大尿斑还是小尿斑都观察到了性别差异。这些数据表明,基因背景和性别可影响小鼠的膀胱功能。在研究基因操作对排尿反射的影响时,这些差异对品系和性别的选择有重大影响。

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