Description

Leber congenital amaurosis (LCA) includes congenital or early-onset blinding diseases, characterized by vision loss together with nystagmus and nonrecordable electroretinogram (ERG). At least 19 genes are associated with LCA. While most LCA is recessive, mutations in the homeodomain transcription factor gene CRX lead to autosomal dominant LCA. The mechanism of CRX-LCA is not understood. Here, we report a new spontaneous mouse mutant carrying a frameshift mutation in Crx (CrxRip). We show that, unlike Crx-/- mouse retina, the dominant Crx c.763del1 mutation in CrxRip results in congenital blindness with complete loss of ERG, yet the photoreceptors do not degenerate. Dominant CRX frameshift mutations associated with LCA mimic the CrxRip phenotype that can be rescued by Crx. RNA-Seq profiling reveals progressive and complete loss of rod differentiation factor Nrl in CrxRip, while residual Nrl remains in Crx-/- retina. Moreover, Nrl partially restores the rod phenotype in CrxRip/+ mice. We show that the binding of Otx2 to Nrl promoter is obliterated in CrxRip mutant, and ectopic Otx2 can rescue the rod phenotype. Therefore, Otx2 is required to maintain Nrl expression in developing rods to consolidate rod fate. Our studies provide the mechanism of congenital blindness caused by dominant CRX mutations and should assist in therapeutic design. Overall design: Retinal samples were harvested from WT, CrxRip/+, CrxRip/Rip, Crx-/- and Nrl-/- retina at postnatal days 2 and 21 for whole transcriptome sequencing (RNAseq). Each sample included 2 independent frozen retina and experiments were performed in duplicates. RNA-seq transcriptome libraries were constructed from 1 µg of total RNA.

Publication Title

OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness.

Sample Metadata Fields

No sample metadata fields

Description

Search for transcripts encoding secreted proteins whose expression are highly induced after phlebotomy.

Publication Title

Identification of erythroferrone as an erythroid regulator of iron metabolism.

Sample Metadata Fields

Sex, Age, Specimen part, Time

Description

Hfe disruption in the mouse leads to experimental hemochromatosis by a mechanism which remains elusive. Evidence for at least five modifier genes has been obtained. These account for the higher iron load of Hfe-deficient D2 mice compared to B6 mice. Gene expression profling was used to clarify the mechanism of Hfe action and to identify potential modifier genes.

Publication Title

Gene expression profiling of Hfe-/- liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers.

Sample Metadata Fields

No sample metadata fields

Description

The Gata2 transcription factor is a pivotal regulator of hematopoietic stem cell (HSC) development and maintenance. Gata2 functions in the embryo during endothelial cell to hematopoietic cell transition (EHT) to affect hematopoietic cluster, HPC and HSC formation. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study we generate a Gata2 Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. Overall design: Gata2Venus- HPCs 1 replicate, Gata2Venus+ HPCs 1 replicate

Publication Title

Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors.

Sample Metadata Fields

Specimen part, Cell line, Subject

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.

Sample Metadata Fields

Specimen part, Treatment

Description

Expression profiling of from Top2 knokout and ICRF-193 treated neurons reveals a significant number of genes that are transcriptionally deregulated

Publication Title

Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.

Sample Metadata Fields

Specimen part, Treatment

Description

Publication Title

Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.

Sample Metadata Fields

No sample metadata fields

Description

Analysis of integrin alpha7 transgenic mice skeletal muscle transcription profiles comparing to wild type controls. Integrin alpha7 is the major laminin binding integrin in muscle cells. Enhancing its expression has been demonstrated to alleviate pathology in a murine model of Duchenne muscular dystrophy. Results of this study provide insights into the effects of increasing integrin alpha7 expression on skeletal muscle transcription and physiology in vivo. This analysis also evaluates any potential possible side effects associate with enhancing integrin alpha7 in skeletal muscle.

Publication Title

Increasing alpha 7 beta 1-integrin promotes muscle cell proliferation, adhesion, and resistance to apoptosis without changing gene expression.

Sample Metadata Fields

Sex, Age, Specimen part

Description

Androgens are a prequisite for the development of human prostate and prostate cancer. Androgen action is mediated via androgen receptor. Androgen ablation therapy is used for the treatment of metastasized prostate cancer. The aim of the study was to identify genes differentially expressed in benign human prostate, prostate cancer and in prostate tissue three days after castration. These genes are potential diagnostic and therapeutic targets for prostate cancer and benign prostatic hyperplasia.

Publication Title

Identification of androgen-regulated genes in human prostate.

Sample Metadata Fields

Specimen part, Disease, Treatment

Description

Monastrol treatment of Leishmania donovani infected macrophages

Publication Title

A member of the Ras oncogene family, RAP1A, mediates antileishmanial activity of monastrol.

Sample Metadata Fields

Specimen part, Disease, Treatment