Analysis of the Hoxa5(-/-) mutants has revealed the critical role of Hoxa5 in survival, specification of axial identity, and ontogeny of organs, including the respiratory tract. The presence of the selection cassette in the original Hoxa5(-/-) mutation may interfere with the interpretation of the phenotypes. To circumvent this aspect and to bypass the lethality of the Hoxa5 mutation, we have designed a conditional approach and generated Hoxa5 allelic variants. The conditional allele (Hoxa5(floxed)) behaves as a wild-type allele. In contrast, both the Hoxa5(Delta) and the Hoxa5(floxneo) alleles are characterized by the loss of the functional transcript and protein, the lethality due to lung defects and the skeletal homeotic transformations similar to those of the Hoxa5(-/-) mutants. Analysis of neighboring Hox gene expression patterns in the Hoxa5 mutants produced further confirmed that the Hoxa5 allelic variants are true null alleles.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/dvg.20292 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Loss of Hoxa5 function affects Hox gene expression in different biological contexts.
Sci Rep
December 2024
Centre de Recherche sur le Cancer de L'Université Laval, Centre de Recherche du CHU de Québec-Université Laval (Oncology), 1401, 18e Rue, Québec, QC, G1J 1Z4, Canada.
Hoxa5 plays numerous roles in development, but its downstream molecular effects are mostly unknown. We applied bulk RNA-seq assays to characterize the transcriptional impact of the loss of Hoxa5 gene function in seven different biological contexts, including developing respiratory and musculoskeletal tissues that present phenotypes in Hoxa5 mouse mutants. This global analysis revealed few common transcriptional changes, suggesting that HOXA5 acts mainly via the regulation of context-specific effectors.
View Article and Find Full Text PDFAssociation of HLA-E single nucleotide polymorphisms with human myeloid leukemia.
HLA
April 2024
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
Single nucleotide polymorphisms (SNPs) of HLA-E are related to the occurrence of many diseases, but their functions remain unclear. In this study, the function of SNPs at HLA-E rs76971248 and rs1264457 on the myeloid leukemia cells was analyzed by a progressive procedure, included genotyping, mRNA transcription, regulatory element, protein expression, and anti-tumor effect. The frequencies of rs76971248 G and rs1264457 G were found higher in myeloid leukemia patients than those in healthy blood donors (p < 0.
View Article and Find Full Text PDFEnhancer Variants Disrupt Transcription Factor Binding And Enhancer Inactivity Drives Pulmonary Hypertension.
Circulation
May 2023
National Heart and Lung Institute, Hammersmith Hospital, Imperial College, London, United Kingdom (R.W., E.V., J.A., C.-N.C., Y.W., A.A., O.D., L.Z., F.S., M.R.W., L.Z., C.J.R.).
Background: Pulmonary arterial hypertension (PAH) is a rare disease characterized by remodeling of the pulmonary arteries, increased vascular resistance, and right-sided heart failure. Genome-wide association studies of idiopathic/heritable PAH established novel genetic risk variants, including conserved enhancers upstream of transcription factor (TF) containing 2 independent signals. SOX17 is an important TF in embryonic development and in the homeostasis of pulmonary artery endothelial cells (hPAEC) in the adult.
View Article and Find Full Text PDFGenetic impacts on thermostability of onco-lncRNA HOTAIR during the development and progression of endometriosis.
PLoS One
October 2021
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
HOTAIR is a well-known long non-coding RNA (lncRNA) involved in various cellular signaling, whereas its functional impacts on endometriosis development are still largely unknown. To this end, six potential functional single nucleotide polymorphisms (SNPs) in HOTAIR, with minor allele frequencies more than 10% in Han population and altered net energy of RNA structures larger than 0.5 kcal/mol, were selected for genotyping study.
View Article and Find Full Text PDFgenes direct elastin network formation during alveologenesis by regulating myofibroblast adhesion.
Proc Natl Acad Sci U S A
November 2018
Department of Internal Medicine, Division of Genetic Medicine, University of Michigan, Ann Arbor, MI 48109-2200;
genes (, , ) are exclusively expressed in the lung mesenchyme during embryogenesis, and the most severe phenotypes result from constitutive loss of function of all three genes. Because triple null mutants exhibit perinatal lethality, the contribution of this paralogous group to postembryonic lung development is unknown. Intriguingly, expression of all three genes peaks during the first 2 weeks after birth, reaching levels far exceeding those measured at embryonic stages, and surviving single and compound mutants exhibit defects in the localization of alveolar myofibroblasts.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!