Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice.
Transcriptome analysis identifies pathways associated with enhanced maternal performance in QSi5 mice.
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DOI：
10.1186/1471-2164-9-197
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发表时间：
2008-04-29
期刊：
影响因子：
4.4
通讯作者：
Williamson, Peter
中科院分区：
文献类型：
--
作者：
Ramanathan, Palaniappan;Martin, Ian C.;Gardiner-Garden, Margaret;Thomson, Peter C.;Taylor, Rosanne M.;Ormandy, Christopher J.;Moran, Christopher;Williamson, Peter
高繁殖力小鼠品系为了解影响母性表现的因素提供了理想的模型。 QSi5近交系小鼠因其高繁殖力和低窝间间隔而被选择，并且与其他近交系相比，在断奶大量后代方面非常成功。产后幼仔体重增加用于估计乳腺产量并比较 QSi5 小鼠与 CBA 小鼠的表现。与 CBA 小鼠相比，QSi5 小鼠在哺乳期前八天的累计窝重和个体幼仔体重增加明显更高。对 QSi5 小鼠怀孕期间乳腺的形态计量分析显示，与 CBA 小鼠相比，其导管侧分支增加了 150%（P < 0.001）。对这两个菌株的转录谱进行本体论和通路分类，发现了涉及许多通路的基因富集，包括 MAPK、紧密连接、胰岛素信号传导和 Wnt 信号传导。其中 11 个基因，包括来自 MAPK 信号通路的 6 个基因，被鉴定为与产后生长相关。此外，Wnt 信号转导的正调节因子（包括 Wnt4、Csnk2a1 和 Smad4）在 QSi5 菌株谱中代表性过高，而负调节因子（包括 Dkkl1、Ppp2r1a 和 Nlk）则代表性不足。这些发现与 Wnt 和 MAPK 信号通路在导管形态发生和小叶肺泡发育中的作用一致，表明 QSi5 小鼠的活性增强。在紧密连接通路的 12 个基因中发现了类似的表型一致性模式，但胰岛素信号基因并未出现这种模式。在一组差异表达的印记基因中，两个抑制通过 IGF 信号通路诱导的生长的母体印记基因 Grb10 和 Igf2r 在 QSi5 小鼠中的代表性不足。而 Peg3 和 Plagl1 这两种促进新生儿生长的父系印记基因在 QSi5 小鼠中出现过多。我们提出，涉及乳腺发育和乳汁分泌的至少三个主要信号通路（即 Wnt、MAPK 和紧密连接通路）的联合作用，有助于 QSi5 小鼠优异的母体表现表型。此外，印记基因 Peg3、Plagl1、Grb10 和 Igf2r 的有利表达模式也可能有所贡献。
Highly fecund mouse strains provide an ideal model to understand the factors affecting maternal performance. The QSi5 inbred strain of mice was selected for high fecundity and low inter-litter interval, and is very successful at weaning large numbers of offspring when compared to other inbred strains. Post-natal pup weight gain was used to estimate mammary gland output and to compare the performance of QSi5 mice to CBA mice. Cumulative litter weights and individual pup weight gain was significantly higher throughout the first eight days of lactation in QSi5 mice compared to CBA mice. Morphometric analysis of mammary glands during pregnancy in QSi5 mice revealed a 150 percent greater ductal side branching compared to CBA mice (P < 0.001). Ontology and pathway classification of transcript profiles from the two strains identified an enrichment of genes involved in a number of pathways, including the MAPK, tight junction, insulin signalling and Wnt signalling. Eleven of these genes, including six genes from the MAPK signalling pathway, were identified as associated with postnatal growth. Further, positive mediators of Wnt signalling, including Wnt4, Csnk2a1 and Smad4, were over-represented in the QSi5 strain profile, while negative regulators, including Dkkl1, Ppp2r1a and Nlk, were under-represented. These findings are consistent with the role of Wnt and MAPK signalling pathway in ductal morphogenesis and lobuloalveolar development suggesting enhanced activity in QSi5 mice. A similar pattern of phenotype concordance was seen amongst 12 genes from the tight junction pathway, but a pattern did not emerge from the insulin signalling genes. Amongst a group of differentially expressed imprinted genes, two maternal imprinted genes that suppress growth induced via the IGF signalling pathway, Grb10 and Igf2r, were under-represented in QSi5 mice. Whereas Peg3 and Plagl1, both paternally imprinted genes that enhance neonatal growth, were over-represented in QSi5 mice. We propose that the combined action of at least three major signalling pathways involved in mammary gland development and milk secretion, namely Wnt, MAPK and tight junction pathways, contribute to the superior maternal performance phenotype in QSi5 mice. Additionally, favourable expression patterns of the imprinted genes Peg3, Plagl1, Grb10 and Igf2r may also contribute.
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影响因子：
4.8
作者：
Dufresne, AM;Smith, RJ
通讯作者：
Smith, RJ
DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
2.5
作者：
Brennan, KR;Brown, AMC
通讯作者：
Brown, AMC
影响因子：
2.7
作者：
BRADBURY, JM;EDWARDS, PAW;DALE, TC
通讯作者：
DALE, TC
影响因子：
7.7
作者：
Civenni, G;Holbro, T;Hynes, NE
通讯作者：
Hynes, NE
影响因子：
3.6
作者：
Hadsell, DL;Torres, DT;Fiorotto, ML
通讯作者：
Fiorotto, ML