Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from the reproductive tracts of WT, Hoxa9,10,11, and Hoxd9,10,11 mutant mice

ABSTRACT: Hox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions, and their interspersed shared enhancers. In this report, we describe a novel recombineering strategy that was used to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10, and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting mutant mice displayed dramatic homeotic transformations of the reproductive tracts, with uterus anteriorized towards oviduct and the vas deferens anteriorized towards epididymis. The Hoxa9,10,11 mutant mice provided a sensitized genetic background that allowed the discovery of Hoxd9,10,11 reproductive tract patterning function. Both shared and distinct Hox functions were defined. The HoxD genes played a crucial role in the regulation of the uterine immune function. Non-coding nonpolyadenylated RNAs were among the key Hox targets. In addition, we observed a surprising anti-dogmatic posteriorization of the uterine epithelium. Reproductive tracts were collected from WT and Hox mutant mice (n=3/genotype) aged 3-7 months in order to characterize the molecular changes caused by mutation of Hoxa9,10,11 and Hoxd9,10,11. Female mice were staged and collected in diestrus.

ORGANISM(S): Mus musculus

SUBMITTER: Steve Potter

PROVIDER: E-GEOD-41993 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts.

Raines Anna M AM Adam Mike M Magella Bliss B Meyer Sara E SE Grimes H Leighton HL Dey Sudhansu K SK Potter S Steven SS

Development (Cambridge, England) 20130612 14

Hox genes are key regulators of development. In mammals, the study of these genes is greatly confounded by their large number, overlapping functions and interspersed shared enhancers. Here, we describe the use of a novel recombineering strategy to introduce simultaneous frameshift mutations into the flanking Hoxa9, Hoxa10 and Hoxa11 genes, as well as their paralogs on the HoxD cluster. The resulting Hoxa9,10,11 mutant mice displayed dramatic synergistic homeotic transformations of the reproducti ...[more]

PMID: 23760953

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Project description:Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. A total of 8 samples were used and analyzed by disease state. Endometrial samples from hysterectomy specimens in proliferative phase of menstrual cycle from symptomatic women with pathologically-confirmed diffuse adenomyosis were compared with endometrial samples from normo-ovulatory healthy subjects with no endometrial or uterine pathology.

Dataset Information

Expression data from the reproductive tracts of WT, Hoxa9,10,11, and Hoxd9,10,11 mutant mice

Publications

Recombineering-based dissection of flanking and paralogous Hox gene functions in mouse reproductive tracts.

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