Standardized, systemic phenotypic analysis of Slc12a1I299F mutant mice.
Standardized, systemic phenotypic analysis of Slc12a1I299F mutant mice.
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DOI：
10.1186/s12929-014-0068-0
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发表时间：
2014-08-02
影响因子：
11
通讯作者：
Aigner B
中科院分区：
文献类型：
--
作者：
Kemter E;Rathkolb B;Becker L;Bolle I;Busch DH;Dalke C;Elvert R;Favor J;Graw J;Hans W;Ivandic B;Kalaydjiev S;Klopstock T;Rácz I;Rozman J;Schrewe A;Schulz H;Zimmer A;Fuchs H;Gailus-Durner V;Hrabe de Angelis M;Wolf E;Aigner B
I型Bartter综合征是一种隐性人类肾病，由编码Na+-K+-2Cl−协同转运蛋白NKCC 2的SLC 12 A1基因的功能缺失突变引起。我们最近建立了突变小鼠品系Slc 12 a1 I299 F，其肾脏缺陷与这种遗传性人类疾病的迟发性表现高度相似。除了肾脏缺陷外，在纯合子突变小鼠中还发现了低血压和骨质减少，这些在人类中也有描述。除了在肾脏中的强表达外，NKCC 2还显示在啮齿动物的其他组织中表达，即胃肠道、胰腺β细胞以及耳、鼻组织和眼的特定隔室。要检查，如果除了肾脏缺陷，进一步的器官系统和/或代谢途径的影响，由Slc 12 a1 I299 F突变的主要或次要影响，我们描述了一个标准化的，系统的表型分析的突变小鼠品系Slc 12 a1 I299 F在德国小鼠诊所。在4-6月龄时测试Slc 12 a1 I299 F纯合突变小鼠和作为对照的Slc 12 a1 I299 F杂合突变同窝小鼠。除了已经发表的血压和骨代谢的变化外，发现Slc 12 a1 I299 F纯合突变小鼠的体重和脂肪含量显著降低，这是新的表型。小的额外影响包括纯合子突变体雄性的轻度红细胞减少性贫血以及纯合子突变体雌性的轻度痛觉过敏。对于其他功能，如免疫学、肺功能和神经学，未观察到明显的变化。在该系统性分析中，除了描述了Slc 12 a1表达的肾脏之外，没有出现Slc 12 a1 I299 F突变对器官的明确主要影响。另一方面，在携带SLC 12 A1突变的人类中，也可能出现肾脏病变的额外和/或继发长期效应。
Type I Bartter syndrome is a recessive human nephropathy caused by loss-of-function mutations in the SLC12A1 gene coding for the Na+-K+-2Cl− cotransporter NKCC2. We recently established the mutant mouse line Slc12a1I299F exhibiting kidney defects highly similar to the late-onset manifestation of this hereditary human disease. Besides the kidney defects, low blood pressure and osteopenia were revealed in the homozygous mutant mice which were also described in humans. Beside its strong expression in the kidney, NKCC2 has been also shown to be expressed in other tissues in rodents i.e. the gastrointestinal tract, pancreatic beta cells, and specific compartments of the ear, nasal tissue and eye. To examine if, besides kidney defects, further organ systems and/or metabolic pathways are affected by the Slc12a1I299F mutation as primary or secondary effects, we describe a standardized, systemic phenotypic analysis of the mutant mouse line Slc12a1I299F in the German Mouse Clinic. Slc12a1I299F homozygous mutant mice and Slc12a1I299F heterozygous mutant littermates as controls were tested at the age of 4–6 months. Beside the already published changes in blood pressure and bone metabolism, a significantly lower body weight and fat content were found as new phenotypes for Slc12a1I299F homozygous mutant mice. Small additional effects included a mild erythropenic anemia in homozygous mutant males as well as a slight hyperalgesia in homozygous mutant females. For other functions, such as immunology, lung function and neurology, no distinct alterations were observed. In this systemic analysis no clear primary effects of the Slc12a1I299F mutation appeared for the organs other than the kidneys where Slc12a1 expression has been described. On the other hand, long-term effects additional and/or secondary to the kidney lesions might also appear in humans harboring SLC12A1 mutations.
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影响因子：
2.5
作者：
Fuchs, Helmut;Gailus-Durner, Valerie;Neschen, Susanne;Adler, Thure;Afonso, Luciana Caminha;Aguilar-Pimentel, Juan Antonio;Becker, Lore;Bohla, Alexander;Calzada-Wack, Julia;Cohrs, Christian;Dewert, Anna;Fridrich, Barbara;Garrett, Lillian;Glasl, Lisa;Goetz, Alexander;Hans, Wolfgang;Hoelter, Sabine M.;Horsch, Marion;Hurt, Anja;Janas, Eva;Janik, Dirk;Kahle, Melanie;Kistler, Martin;Klein-Rodewald, Tanja;Lengger, Christoph;Ludwig, Tonia;Maier, Holger;Marschall, Susan;Micklich, Kateryna;Moeller, Gabriele;Naton, Beatrix;Prehn, Cornelia;Puk, Oliver;Racz, Ildiko;Raess, Michael;Rathkolb, Birgit;Rozman, Jan;Scheerer, Markus;Schiller, Evelyn;Schrewe, Anja;Steinkamp, Ralph;Stoeger, Claudia;Sun, Minxuan;Szymczak, Wilfried;Treise, Irina;Panesso, Ingrid Liliana Vargas;Vernaleken, Alexandra M.;Willershaeuser, Monja;Wolff-Muscate, Annemarie;Zeh, Ramona;Adamski, Jerzy;Beckers, Johannes;Bekeredjian, Raffi;Busch, Dirk H.;Eickelberg, Oliver;Favor, Jack;Graw, Jochen;Hoefler, Heinz;Hoeschen, Christoph;Katus, Hugo;Klingenspor, Martin;Klopstock, Thomas;Neff, Frauke;Ollert, Markus;Schulz, Holger;Stoeger, Tobias;Wolf, Eckhard;Wurst, Wolfgang;Yildirim, Ali Onder;Zimmer, Andreas;de Angelis, Martin Hrabe
通讯作者：
de Angelis, Martin Hrabe
影响因子：
2.7
作者：
Musselman, Teddy M.;Zhang, Zheng;Masilamani, Shyama M. E.
通讯作者：
Masilamani, Shyama M. E.
DOI：
10.1152/ajprenal.00213.2006
发表时间：
2007-05-01
影响因子：
4.2
作者：
Aigner, Bernhard;Rathkolb, Birgit;Wolf, Eckhard
通讯作者：
Wolf, Eckhard
DOI：
10.1097/01.mnh.0000437204.84826.99
发表时间：
2014-01
影响因子：
3.2
作者：
Welling PA
通讯作者：
Welling PA
DOI：
10.1073/pnas.090091297
发表时间：
2000-05-09
影响因子：
11.1
作者：
Takahashi, N;Chernavvsky, DR;Smithies, O
通讯作者：
Smithies, O