Gene expression in LSK cells of C57B/L6, DBA/2J, B.D(Chr5), & D.B(Chr5) mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE21896 | GEO | 2010/05/21
SECONDARY ACCESSION(S): PRJNA126855
REPOSITORIES: GEO
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Project description:These mouse strains differ in absolute numbers of hematopoietic stem cells but differ genetically only at the Chr 5 congenic locus. We used microarray analysis to identify candidate regulators of hematopoietic stem cells based on differential gene expression patterns. Triplicate RNA samples, except for duplicate DBA/2J samples, were isolated from 80,00-137,000 LSK cells from each strain. Each of the 11 samples were analyzed on individual microarrays on two Illumina Sentrix-Mouse 6 Whole Genome Expression Beadhips.
2010-05-21 | E-GEOD-21896 | biostudies-arrayexpress
Project description:These mouse strains differ in absolute numbers of hematopoietic stem cells but differ genetically only at the Chr 5 congenic locus. We used microarray analysis to identify candidate regulators of hematopoietic stem cells based on differential gene expression patterns.
2010-05-21 | GSE21905 | GEO
Project description:These mouse strains differ in absolute numbers of hematopoietic stem cells but differ genetically only at the Chr 5 congenic locus. We used microarray analysis to identify candidate regulators of hematopoietic stem cells based on differential gene expression patterns. Triplicate RNA samples were isolated from 500,00-800,000 Lineage negative bone marrow cells from each strain. Each of the six samples were analyzed on 6 separate MG 430 2.0 Affymetrix Microarray Chips.
2010-06-08 | E-GEOD-21905 | biostudies-arrayexpress
Project description:We previously utilized interval-specific congenic lines derived from C57BL/6J (B6) and DBA/2J (D2) alleles to fine map a quantitative trait locus (QTL) influencing methamphetamine (MA)- induced locomotor activity. We identified a 0.23 MB critical interval on chromosome 11 containing only two protein coding genes, Rufy1 and Hnrnph1. Notably, Rufy1 contains three missense SNPs and Hnrnph1 contains 1 SNP near the 5’ UTR. In an effort to identify the molecular mechanisms that bridge genetic variation with behavior, we conducted transcriptome analysis via mRNA sequencing (RNA-seq) in a B6.D2 congenic line (chr.11: 50-60 Mb) that captures the QTL. There was an overrepresentation of cis-regulated, differentially expressed genes within the congenic interval (4 out of 92 differentially expressed genes; FDR < 0.05) and widespread genomic regulation on all autosomes.
2015-12-11 | GSE66366 | GEO
Project description:To compare phospholipid profiles [phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylinositol (PI)] of normotensive and hypertensive aqueous humor (AH) from DBA/2J and compare them with phospholipid profiles of DBA/2J-Gpnmb(+)/SjJ mice.AH was obtained from young-normotensive DBA/2J, old -hypertensive DBA/2J mice, young and old DBA/2J-Gpnmb(+)/SjJ mice (aging control). Lipids were extracted using modified Bligh and Dyer method and subjected to mass spectrometric identification using appropriate class-specific lipid standards and ratiometric quantification. Corresponding aqueous phase (of extraction) protein concentrations were measured using Bradford method.The total amount of phospholipids showed a decrease in the hypertensive state compared to normotensive state. The total PE and total PS contributed over 50% of the total amount. Total PS showed a remarkable decrease in hypertensive compared to normotensive state. In contrast, total PE in the hypertensive stage presented an increase in amount. Unique lipid species were found encompassing all four phospholipid classes in normotensive as well as in the hypertensive state. Several phospholipid species were found common to both states but with remarkable differences in amount in individual states. The ratio of lysophospholipids to total phospholipids is significantly reduced in the hypertensive state. Commensurate with reduced level of lysophospholipids, we found an increased level of lysophospholipase D (Autotaxin) in the hypertensive state. The difference of total phospholipids between young and old was 35.4% in DBA/2J group but 10% in DBA/2J-Gpnmb(+)/SjJ mice.The significant change of phospholipids including lysophospholipids was found commensurate with the elevated intraocular pressure (IOP).
| S-EPMC4430412 | biostudies-literature
Project description:Recent advances in mouse genomics have revealed considerable variation in the form of single-nucleotide polymorphisms (SNPs) among common inbred strains. This has made it possible to characterize closely related strains and to identify genes that differ; such genes may be causal for quantitative phenotypes. The mouse strains DBA/1J and DBA/2J differ by just 5.6% at the SNP level. These strains exhibit differences in a number of metabolic and lipid phenotypes, such as plasma levels of triglycerides (TGs) and HDL. A cross between these strains revealed multiple quantitative trait loci (QTLs) in 294 progeny. We identified significant TG QTLs on chromosomes (Chrs) 1, 2, 3, 4, 8, 9, 10, 11, 12, 13, 14, 16, and 19, and significant HDL QTLs on Chrs 3, 9, and 16. Some QTLs mapped to chromosomes with limited variability between the two strains, thus facilitating the identification of candidate genes. We suggest that Tshr is the QTL gene for Chr 12 TG and HDL levels and that Ihh may account for the TG QTL on Chr 1. This cross highlights the advantage of crossing closely related strains for subsequent identification of QTL genes.
| S-EPMC2834962 | biostudies-literature
Project description:Cranial base growth plates are important centers of longitudinal growth in the skull and are responsible for the proper anterior placement of the face and the stimulation of normal cranial vault development. We report that the presphenoidal synchondrosis (PSS), a midline growth plate of the cranial base, closes in the DBA/2J mouse strain but not in other common inbred strains. We investigated the genetics of PSS closure in DBA/2J mice by evaluating F1, F1 backcross, and/or F1 intercross offspring from matings with C57BL/6J and DBA/1J mice, whose PSS remain open. We observed that PSS closure is genetically determined, but not inherited as a simple Mendelian trait. Employing a genome-wide SNP array, we identified a region on chromosome 11 in the C57BL/6J strain that affected the frequency of PSS closure in F1 backcross and F1 intercross offspring. The equivalent region in the DBA/1J strain did not affect PSS closure in F1 intercross offspring. We conclude that PSS closure in the DBA/2J strain is complex and modified by different loci when outcrossed with C57BL/6J and DBA/1J mice.
| S-EPMC3560942 | biostudies-literature
Project description:PurposeGlaucoma is a complex disease with major risk factors including advancing age and increased intraocular pressure (IOP). Dissecting these earliest events will likely identify new avenues for therapeutics. Previously, we performed transcriptional profiling in DBA/2J (D2) mice, a widely used mouse model relevant to glaucoma. Here, we use these data to identify and test regulators of early gene expression changes in DBA/2J glaucoma.MethodsUpstream regulator analysis (URA) in Ingenuity Pathway Analysis was performed to identify potential master regulators of differentially expressed genes. The function of one putative regulator, mesenchyme homeobox 2 (Meox2), was tested using a combination of genetic, biochemical, and immunofluorescence approaches.ResultsURA identified Meox2 as a potential regulator of early gene expression changes in the optic nerve head (ONH) of DBA/2J mice. Meox2 haploinsufficiency did not affect the characteristic diseases of the iris or IOP elevation seen in DBA/2J mice but did cause a significant increase in the numbers of eyes with axon damage compared to controls. While young mice appeared normal, aged Meox2 haploinsufficient DBA/2J mice showed a 44% reduction in MEOX2 protein levels. This correlated with modulation of age- and disease-specific vascular and myeloid alterations.ConclusionsOur data support a model whereby Meox2 controls IOP-dependent vascular remodeling and neuroinflammation to promote axon survival. Promoting these earliest responses prior to IOP elevation may be a viable neuroprotective strategy to delay or prevent human glaucoma.
| S-EPMC6676925 | biostudies-literature
Project description:We previously utilized interval-specific congenic lines derived from C57BL/6J (B6) and DBA/2J (D2) alleles to fine map a quantitative trait locus (QTL) influencing methamphetamine (MA)- induced locomotor activity. We identified a 0.23 MB critical interval on chromosome 11 containing only two protein coding genes, Rufy1 and Hnrnph1. Notably, Rufy1 contains three missense SNPs and Hnrnph1 contains 1 SNP near the 5â UTR. In an effort to identify the molecular mechanisms that bridge genetic variation with behavior, we conducted transcriptome analysis via mRNA sequencing (RNA-seq) in a B6.D2 congenic line (chr.11: 50-60 Mb) that captures the QTL. There was an overrepresentation of cis-regulated, differentially expressed genes within the congenic interval (4 out of 92 differentially expressed genes; FDR < 0.05) and widespread genomic regulation on all autosomes. For this study, 3mm punches from both striatal hemispheres were collected and pooled from 16 mice (8 controls and 8 B6.D2 congenics), and RNA was extracted and prepared for cDNA library preparation using the Illumina TruSeq (oligo-dT; 50bp single-end reads). Samples 1-16, consisting of alternating B6 and B6.D2 congenics were run in four lanes total, with samples 1-8 run in duplicate across lanes 5 and 6 and samples 9-16 acorss lanes 7 and 8, respectively. Raw samples provided are labeled with the "CB-" prefix, followed by the sample number and the lane that it was run in is described at the tail end as "_L00#" with # being either lane 5, 6, 7 or 8. In this study, all odd samples (e.g. CB-1,3,5 etc.) are C57BL/6J littermate controls, while all even samples are B6.D2 congenics. Note that the lane 7 replicate for Sample CB-13 (CB-13_L007.fastq.gz) was not processed due to technical difficulties with the file.
2015-12-11 | E-GEOD-66366 | biostudies-arrayexpress
Project description:PurposeThe optomotor reflex of DBA/2J (D2), DBA/2J-Gpnmb+ (D2-Gpnmb+), and C57BL/6J (B6) mouse strains was assayed, and the retinal ganglion cell (RGC) firing patterns, direction selectivity, vestibulomotor function and central vision was compared between the D2 and B6 mouse lines.MethodsIntraocular pressure (IOP) measurements, real-time PCR, and immunohistochemical analysis were used to assess the time course of glaucomatous changes in D2 retinas. Behavioral analyses of optomotor head-turning reflex, visible platform Morris water maze and Rotarod measurements were conducted to test vision and vestibulomotor function. Electroretinogram (ERG) measurements were used to assay outer retinal function. The multielectrode array (MEA) technique was used to characterize RGC spiking and direction selectivity in D2 and B6 retinas.ResultsProgressive increase in IOP and loss of Brn3a signals in D2 animals were consistent with glaucoma progression starting after 6 months of age. D2 mice showed no response to visual stimulation that evoked robust optomotor responses in B6 mice at any age after eye opening. Spatial frequency threshold was also not measurable in the D2-Gpnmb+ strain control. ERG a- and b-waves, central vision, vestibulomotor function, the spiking properties of ON, OFF, ON-OFF, and direction-selective RGCs were normal in young D2 mice.ConclusionsThe D2 strain is characterized by a lack of optomotor reflex before IOP elevation and RGC degeneration are observed. This behavioral deficit is D2 strain-specific, but is independent of retinal function and glaucoma. Caution is advised when using the optomotor reflex to follow glaucoma progression in D2 mice.
| S-EPMC3175994 | biostudies-literature