Polymorphisms in the interleukin-4 receptor chain (IL-4R) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target and tissue-specific manner to mediate heightened expression of a subset of IL-4 and IL-13responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rdependent signaling.
Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.
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Polycomb repressive complex 2 is required for MLL-AF9 leukemia.
Specimen part, Disease, Disease stage
View SamplesWe evaluated gene expression changes in murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of homozygous conditional alleles for Ezh2 or Eed, both of which are components of the Polycomb Repressive Complex2.
Polycomb repressive complex 2 is required for MLL-AF9 leukemia.
Specimen part, Disease, Disease stage
View SamplesWe evaluated gene expression changes in secondary recipient murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of a homozygous conditional allele for Ezh2, a component of the Polycomb Repressive Complex2.
Polycomb repressive complex 2 is required for MLL-AF9 leukemia.
Specimen part, Disease, Disease stage
View SamplesThe lung host immune responses following M.tuberculosis infection in the mouse model of tuberculosis were assayed by studying the gene expression profiles at day 0, day 12, 15 and 21 post infection
Profiling early lung immune responses in the mouse model of tuberculosis.
Specimen part, Time
View SamplesRod and cone photoreceptors in mammalian retina are generated from common pool(s) of neuroepithelial progenitors. NRL, CRX and NR2E3 are key transcriptional regulators that control photoreceptor differentiation. Mutations in NR2E3, a rod-specific orphan nuclear receptor, lead to loss of rods, increased density of S-cones, and supernormal S-cone-mediated vision in humans. To better understand its in vivo function, NR2E3 was expressed ectopically in the Nrl-/- retina, where post-mitotic precursors fated to be rods develop into functional S-cones similar to the human NR2E3 disease. Expression of NR2E3 in the Nrl-/- retina completely suppressed cone differentiation and resulted in morphologically rod-like photoreceptors, which were not functional. Gene profiling of FACS-purified photoreceptors confirmed the role of NR2E3 as a strong suppressor of cone genes and an activator of a subset of rod genes (including rhodopsin) in vivo. Ectopic expression of NR2E3 in cone precursors and differentiating S-cones of wild type retina also generates rod-like cells. The dual regulatory function of NR2E3 is not dependent upon the presence of NRL and/or CRX, but on the timing and level of its expression. Our studies reveal a critical role of NR2E3 in establishing functional specificity of post-mitotic photoreceptor precursors during retinal neurogenesis.
In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development.
Sex, Specimen part
View SamplesBeyond the DNA sequence difference between humans and closely related apes, there are large differences in the environments that these species experience. One prominent example for this is diet. The human diet diverges from those of other primates in various aspects, such as having a high calorie and protein content, as well as being cooked. Here, we used a laboratory mouse model to identify gene expression differences related to dietary differences.
Human and chimpanzee gene expression differences replicated in mice fed different diets.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Age, Specimen part
View SamplesMouse adult female brains cortex (C57BL/6, Charles River Laboratories, Inc.) was isolated and stored immediately at -80C. Subsequently, the mRNA (15g) was isolated using TRIzol Reagent and MicroFastTrack 2.0 Kit (Invitrogen). A Sample of 5g was assessed on Affymetrix Mouse 430.2 array. Aliquots from the leftovers of the same cortical mRNA were diluted to single-cell RNA levels (0.1, 1, and 10 pg) and independently aRNA amplified for a total of 2 and 4 rounds and assessed on Affymetrix Mouse 430.2 arrays.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Specimen part
View SamplesGene expressions of murine germinal center and naive B cells on Affymetrix platform
Multiple transcription factor binding sites predict AID targeting in non-Ig genes.
No sample metadata fields
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