Metabolic characterization of a mouse deficient in all known leptin receptor isoforms.
Metabolic characterization of a mouse deficient in all known leptin receptor isoforms.
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DOI：
10.1007/s10571-009-9427-x
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发表时间：
2010-01
影响因子：
4
通讯作者：
Bartfai, Tamas
中科院分区：
文献类型：
--
作者：
Osborn, Olivia;Sanchez-Alavez, Manuel;Brownell, Sara E.;Ross, Brendon;Klaus, Joe;Dubins, Jeffrey;Beutler, Bruce;Conti, Bruno;Bartfai, Tamas
我们描述了一种新产生的肥胖小鼠模型，一种小鼠品系缺乏所有五种先前描述的瘦素受体同种异构体。这些转基因小鼠，被命名为db333/db333小鼠，通过ENU突变筛选鉴定，在编码瘦素受体的db基因的第7外显子上携带一个点突变，导致过早停止密码子（Y333Stop）和缺乏STAT信号域的基因产物。db333/db333小鼠早在4周龄时体重就与野生型偏离（P<0.05），呈现病态肥胖表型。为了确定瘦素受体短异构体在这种代谢表型中的作用，我们对db333/db333小鼠进行了广泛的代谢表征，并与仅缺乏瘦素受体长异构体的db/db小鼠进行了充分表征。Db333 / Db333小鼠具有与先前描述的其他瘦素受体转基因小鼠相似的内分泌和代谢参数，包括仅缺乏瘦素受体长异构体的db/db小鼠。然而，与db/db小鼠相比，db333/db333小鼠表现出更高的体重、胰岛素水平、更低的产氧量、二氧化碳产量、呼吸效率比和温度的微妙趋势，这表明短亚型可能在能量稳态中发挥了额外的作用。
We have characterized a newly generated mouse model of obesity, a mouse strain deficient in all five previously described leptin receptor isoforms. These transgenic mice, named the db333/db333 mice, were identified from an ENU mutagenesis screen and carry a point mutation in the seventh exon of the db gene encoding the leptin receptor, resulting in a premature stop codon (Y333Stop) and gene product that lacks STAT signaling domains. db333/db333 mice have a morbidly obese phenotype, with body weights diverging from wild-type as early as 4 weeks of age (P<0.05). To determine the contribution of the short isoforms of the leptin receptor in this metabolic phenotype we performed an extensive metabolic characterization of the db333/db333 mouse in relation to the well characterized db/db mouse lacking only the long form of the leptin receptor. db333/db333 mice have similar endocrine and metabolic parameters as previously described in other leptin receptor transgenic mice including db/db mice that lack only the long isoform of the leptin receptor. However, db333/db333 mice show a subtle trend towards higher body weight, insulin levels, lower oxygen production, carbon dioxide production, respiratory efficiency ratio and temperature than db/db mice suggesting the short isoforms may play an additional role in energy homeostasis.
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影响因子：
4.8
作者：
Heiman, ML;Ahima, RS;Flier, JS
通讯作者：
Flier, JS
DOI：
10.1073/pnas.93.13.6231
发表时间：
1996-06-25
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
2.2
作者：
Hwa, JJ;Ghibaudi, L;Strader, CD
通讯作者：
Strader, CD
影响因子：
64.5
作者：
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通讯作者：
Morgenstern, JP