New Candidate Genes Identified for Controlling Mouse Gonadal Sex Determination and the Early Stages of Granulosa and Sertoli Cell Differentiation
New Candidate Genes Identified for Controlling Mouse Gonadal Sex Determination and the Early Stages of Granulosa and Sertoli Cell Differentiation
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DOI：
10.1095/biolreprod.109.079822
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发表时间：
2010-02-01
影响因子：
3.6
通讯作者：
Eicher, Eva M.
中科院分区：
文献类型：
--
作者：
Bouma, Gerrit J.;Hudson, Quanah J.;Eicher, Eva M.
哺乳动物性腺性别决定（GSD）基因在一个独特的体细胞群中表达，这些体细胞在XX性腺中分化为颗粒细胞或在XY性腺中分化为支持细胞。在性腺发育的最早阶段有效分离这些体细胞支持细胞（SSC）的能力将有助于鉴定1）可能参与不明原因的异常性腺发育的新的候选GSD基因和2）参与颗粒细胞和支持细胞分化的最早阶段的基因。我们报告了一种携带两种转基因的独特小鼠的发展，这两种转基因使XX和XY小鼠早在胚胎第11.5天（E11.5）就能区分开来，并允许从未分化（E11.5）和早期分化（E12.5）的胎儿性腺中分离SSC。使用小鼠基因组430v2.0基因芯片（Affyestival）鉴定在XX和XY分离的SSC中表现出性二态表达模式的转录物。该分析揭示了先前未鉴定的性二态性转录本，包括低水平表达的基因，如Sry，一种在其他微阵列研究中未鉴定的基因。多基因实时荧光PCR分析证实53个基因在胎儿性腺中以性二态模式表达，整装原位杂交分析证实4930563E18Rik、Pld 1和Sprr 2d在XX性腺中表达，Fbln 2、Ppargc1a和Scrn 1在XY性腺中表达。总之，这些数据提供了一个全面的资源，为基因的时空表达模式的一部分，哺乳动物胎儿性腺发育的早期阶段，包括颗粒细胞和支持细胞的发展的遗传网络。
Mammalian gonadal sex-determining (GSD) genes are expressed in a unique population of somatic cells that differentiate into granulosa cells in XX gonads or Sertoli cells in XY gonads. The ability to efficiently isolate these somatic support cells (SSCs) during the earliest stages of gonad development would facilitate identifying 1) new candidate GSD genes that may be involved in cases of unexplained abnormal gonad development and 2) genes involved in the earliest stages of granulosa and Sertoli cell differentiation. We report the development of a unique mouse carrying two transgenes that allow XX and XY mice to be distinguished as early as Embryonic Day 11.5 (E11.5) and allow SSCs to be isolated from undifferentiated (E11.5) and early differentiated (E12.5) fetal gonads. The Mouse Genome 430v2.0 GeneChip (Affymetrix) was used to identify transcripts exhibiting a sexual dimorphic expression pattern in XX and XY isolated SSCs. The analysis revealed previously unidentified sexually dimorphic transcripts, including low-level expressed genes such as Sry, a gene not identified in other microarray studies. Multigene real-time PCR analysis of 57 genes verified that 53 were expressed in fetal gonads in a sexually dimorphic pattern, and whole-mount in situ hybridization analysis verified 4930563E18Rik, Pld1, and Sprr2d are expressed in XX gonads, and Fbln2, Ppargc1a, and Scrn1 are expressed in XY gonads. Taken together, the data provide a comprehensive resource for the spatial-temporal expression pattern of genes that are part of the genetic network underlying the early stages of mammalian fetal gonadal development, including the development of granulosa and Sertoli cells.