Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line.
Precise pattern of recombination in serotonergic and hypothalamic neurons in a Pdx1-cre transgenic mouse line.
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DOI：
10.1186/1423-0127-17-82
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发表时间：
2010-10-17
影响因子：
11
通讯作者：
Tecott LH
中科院分区：
文献类型：
--
作者：
Honig G;Liou A;Berger M;German MS;Tecott LH
多细胞生物体的特征在于形态上不同和功能上特化的细胞类型的显著多样性。在特定细胞群体中操纵基因表达的转基因技术对于阐明这些细胞群体的发育和功能非常有用。鉴于胰腺β细胞和肾上腺素能神经元之间发育基因表达的显著相似性，我们研究了广泛使用的小鼠系Pdx 1-cre（正式名称，Tg（Ipf 1-cre）89.1Dam）神经系统中Cre介导的重组模式，其中Cre重组酶的表达由pdx 1（胰腺十二指肠同源框1）基因上游的调控元件驱动。将pdx 1-creCre/0基因型的单（半合子）转基因小鼠与单（半合子）转基因报告小鼠（Z/EG和rosa 26 R系）交配。在e9.5、e10.5、e11.5、e16.5和成体发育阶段，使用整体安装和切片组织学制备物检查后代的发育模式。除了先前报道的胰腺重组外，还观察到发育中的神经系统和内耳形成中的重组。在中枢神经系统中，我们观察到腹侧脑干和间脑中神经元祖细胞的高度特异性重组模式。在头端脑干（r1-r2），重组发生在新生的多巴胺能神经元。在尾侧脑干，重组发生在非多巴胺能细胞。在成年人中，这导致报告基因表达的绝大多数前脑投射神经元（位于中缝背侧核和中缝正中核），但没有脊髓投射神经元的中缝尾侧核。在成人尾侧脑干，报告基因表达广泛分布于下橄榄核。在成人下丘脑，重组观察弓状核和背内侧下丘脑。在中枢神经系统的任何其他区域均未观察到震颤。未观察到内源性pdx 1的神经元表达。Pdx 1-cre小鼠系和相应转基因中所含的调控元件可能是一种有价值的工具，用于对发育中的前脑投射神经元和其他几种独特的神经元亚群进行靶向遗传操作。这些结果表明，研究人员采用这种小鼠系胰腺功能的研究应考虑中枢神经系统的影响对所得表型的可能贡献。
Multicellular organisms are characterized by a remarkable diversity of morphologically distinct and functionally specialized cell types. Transgenic techniques for the manipulation of gene expression in specific cellular populations are highly useful for elucidating the development and function of these cellular populations. Given notable similarities in developmental gene expression between pancreatic β-cells and serotonergic neurons, we examined the pattern of Cre-mediated recombination in the nervous system of a widely used mouse line, Pdx1-cre (formal designation, Tg(Ipf1-cre)89.1Dam), in which the expression of Cre recombinase is driven by regulatory elements upstream of the pdx1 (pancreatic-duodenal homeobox 1) gene. Single (hemizygous) transgenic mice of the pdx1-creCre/0 genotype were bred to single (hemizygous) transgenic reporter mice (Z/EG and rosa26R lines). Recombination pattern was examined in offspring using whole-mount and sectioned histological preparations at e9.5, e10.5, e11.5, e16.5 and adult developmental stages. In addition to the previously reported pancreatic recombination, recombination in the developing nervous system and inner ear formation was observed. In the central nervous system, we observed a highly specific pattern of recombination in neuronal progenitors in the ventral brainstem and diencephalon. In the rostral brainstem (r1-r2), recombination occurred in newborn serotonergic neurons. In the caudal brainstem, recombination occurred in non-serotonergic cells. In the adult, this resulted in reporter expression in the vast majority of forebrain-projecting serotonergic neurons (located in the dorsal and median raphe nuclei) but in none of the spinal cord-projecting serotonergic neurons of the caudal raphe nuclei. In the adult caudal brainstem, reporter expression was widespread in the inferior olive nucleus. In the adult hypothalamus, recombination was observed in the arcuate nucleus and dorsomedial hypothalamus. Recombination was not observed in any other region of the central nervous system. Neuronal expression of endogenous pdx1 was not observed. The Pdx1-cre mouse line, and the regulatory elements contained in the corresponding transgene, could be a valuable tool for targeted genetic manipulation of developing forebrain-projecting serotonergic neurons and several other unique neuronal sub-populations. These results suggest that investigators employing this mouse line for studies of pancreatic function should consider the possible contributions of central nervous system effects towards resulting phenotypes.
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影响因子：
16.2
作者：
Kim, Jun Chul;Cook, Melloni N.;Carey, Megan R.;Shen, Chung;Regehr, Wade G.;Dymecki, Susan M.
通讯作者：
Dymecki, Susan M.
影响因子：
29
作者：
Fujikura, J;Hosoda, K;Nakao, K
通讯作者：
Nakao, K
DOI：
10.1016/j.bbrc.2005.06.162
发表时间：
2005-09-02
影响因子：
3.1
作者：
Lee, JY;Hennighausen, L
通讯作者：
Hennighausen, L
影响因子：
16.2
作者：
Hoshino, M;Nakamura, S;Nabeshima, YI
通讯作者：
Nabeshima, YI
影响因子：
2.5
作者：
Fujikura, Junji;Hosoda, Kiminori;Nakao, Kazuwa
通讯作者：
Nakao, Kazuwa