Faculty of Veterinary Science, The University of Sydney, New South Wales, Australia.
Physiol Genomics. 2013 Mar 1;45(5):171-81. doi: 10.1152/physiolgenomics.00139.2011. Epub 2013 Jan 2.
Mammary transcriptome analyses across the lactation cycle and transgenic animal studies have identified candidate genes for mammogenesis, lactogenesis and involution; however, there is a lack of information on pathways that contribute to lactation performance. Previously we have shown significant differences in lactation performance, mammary gland histology, and gene expression profiles during lactation [lactation day 9 (L9)] between CBA/CaH (CBA) and the superior performing QSi5 strains of mice. In the present study, we compared these strains at midpregnancy [pregnancy day 12 (P12)] and utilized these data along with data from a 14th generation of intercross (AIL) to develop an integrative analysis of lactation performance. Additional analysis by quantitative reverse transcription PCR examined the correlation between expression profiles of lactation candidate genes and lactation performance across six inbred strains of mice. The analysis demonstrated that the mammary epithelial content per unit area was similar between CBA and QSi5 mice at P12, while differential expression was detected in 354 mammary genes (false discovery rate < 0.1). Gene ontology and functional annotation analyses showed that functional annotation terms associated with cell division and proliferation were the most enriched in the differentially expressed genes between these two strains at P12. Further analysis revealed that genes associated with neuroactive ligand-receptor interaction and calcium signaling pathways were significantly upregulated and positively correlated with lactation performance, while genes associated with cell cycle and DNA replication pathways were downregulated and positively correlated with lactation performance. There was also a significant negative correlation between Grb10 expression and lactation performance. In summary, using an integrative genomic approach we have identified key genes and pathways associated with lactation performance.
乳转录组分析在泌乳周期和转基因动物研究中鉴定了乳腺发生、泌乳和退化的候选基因；然而，对于参与泌乳性能的途径知之甚少。先前，我们已经表明在泌乳[泌乳第 9 天（L9）]期间，CBA/CaH（CBA）和表现更优的 QSi5 品系小鼠之间的泌乳性能、乳腺组织学和基因表达谱存在显著差异。在本研究中，我们在妊娠中期[妊娠第 12 天（P12）]比较了这些品系，并利用这些数据以及第 14 代杂交（AIL）的数据，对泌乳性能进行综合分析。通过定量逆转录 PCR 的额外分析检查了泌乳候选基因的表达谱与六种近交系小鼠的泌乳性能之间的相关性。分析表明，在 P12 时，CBA 和 QSi5 小鼠的单位面积乳腺上皮细胞含量相似，而在 354 个乳腺基因中检测到差异表达（错误发现率<0.1）。基因本体论和功能注释分析表明，与细胞分裂和增殖相关的功能注释术语在这两个品系之间的差异表达基因中最为丰富。进一步分析表明，与神经活性配体-受体相互作用和钙信号通路相关的基因显著上调，并与泌乳性能呈正相关，而与细胞周期和 DNA 复制通路相关的基因下调，并与泌乳性能呈正相关。Grb10 表达与泌乳性能之间也存在显著的负相关。总之，使用综合基因组方法，我们已经确定了与泌乳性能相关的关键基因和途径。
