AI Article Synopsis

  • The HMGA2 protein is crucial for binding DNA and regulating transcription, with its absence causing dwarfism in mice and rabbits.
  • CRISPR/Cas9 was utilized to create a specific mouse model with Hmga2 knocked out, which led to significant reductions in body size and infertility in both male and female mice.
  • Despite the reduction in body size and changes in reproductive organs, Hmga2-/- mice had normal testis histology and showed altered behaviors, indicating HMGA2’s important role in growth regulation and behavioral functions.

Article Abstract

The high mobility group AT-hook 2 (HMGA2) protein works as an architectural regulator by binding AT-rich DNA sequences to induce conformational changes affecting transcription. Genomic deletions disrupting HMGA2 coding sequences and flanking noncoding sequences cause dwarfism in mice and rabbits. Here, CRISPR/Cas9 was used in mice to generate an Hmga2 null allele that specifically disrupts only the coding sequence. The loss of one or both alleles of Hmga2 resulted in reduced body size of 20% and 60%, respectively, compared to wild-type littermates as well as an allometric reduction in skull length in Hmga2-/- mice. Both male and female Hmga2-/- mice are infertile, whereas Hmga2+/- mice are fertile. Examination of reproductive tissues of Hmga2-/- males revealed a significantly reduced size of testis, epididymis, and seminal vesicle compared to controls, and 70% of knock-out males showed externalized penis, but no cryptorchidism was observed. Sperm analyses revealed severe oligospermia in mutant males and slightly decreased sperm viability, increased DNA damage but normal sperm chromatin compaction. Testis histology surprisingly revealed a normal seminiferous epithelium, despite the significant reduction in testis size. In addition, Hmga2-/- mice showed a significantly reduced exploratory behavior. In summary, the phenotypic effects in mouse using targeted mutagenesis confirmed that Hmga2 is affecting prenatal and postnatal growth regulation, male reproductive tissue development, and presents the first indication that Hmga2 function is required for normal mouse behavior. No specific effect, despite an allometric reduction, on craniofacial development was noted in contrast to previous reports of an altered craniofacial development in mice and rabbits carrying deletions of both coding and noncoding sequences at the 5' part of Hmga2.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210324PMC
http://dx.doi.org/10.1093/g3journal/jkab417DOI Listing

Publication Analysis

Top Keywords

hmga2-/- mice
12
hmga2
8
mice
8
noncoding sequences
8
mice rabbits
8
allometric reduction
8
craniofacial development
8
hmga2 deficiency
4
deficiency associated
4
associated allometric
4

Similar Publications

Loss of the glutathione-S-transferases Theta 2 (Gstt2) expression is associated with an improved response to intravesical , Bacillus Calmette-Guérin (BCG) immunotherapy for non-muscle-invasive bladder cancer (NMIBC) patients who receive fewer BCG instillations. To delineate the cause, Gstt2 knockout (KO) and wildtype (WT) C57Bl/6J mice were implanted with tumors before treatment with BCG or saline. RNA was analyzed via single-cell RNA sequencing (scRNA-seq) and real-time polymerase chain reaction (RT-PCR).

View Article and Find Full Text PDF

Background: A controlled type of cell death called ferroptosis is linked to increased reactive oxygen species (ROS), lipid peroxidation, and iron buildup. Furthermore, evidence indicates that ferroptosis may act as an immunogenic form of cell death with potential physiological functions in tumors and immunosuppression. Inducing ferroptosis in tumor cells may have the potential to complement cancer immunotherapy strategies.

View Article and Find Full Text PDF

Atherosclerosis (AS) is a vascular disease associated with endothelial damage, plaque formation, and retinal neovascularization (RNV), leading to visual impairment. Research indicates that vascular endothelial dysfunction, lipid deposition, and inflammatory responses contribute to the formation of plaques and atherosclerotic lesions. Among the common complications, studies have shown that RNV and the molecular mechanisms of AS hold significant clinical importance.

View Article and Find Full Text PDF
Article Synopsis
  • Gastric cancer has a poor prognosis and circRNA_0001860 (circ_0001860) is found to be upregulated in gastric cancer cells, which may indicate its role in cancer development.
  • Experiments showed that knocking down circ_0001860 decreased cell viability, invasion, and altered immune response in gastric cancer cells, suggesting it promotes cancer progression.
  • The findings also suggest that circ_0001860 operates by sponging miR-618 and regulating HMGA2 levels, and its expression is influenced by EIF4A3, highlighting its potential as a therapeutic target.
View Article and Find Full Text PDF

Exploring Testicular Descent: Recent Findings and Future Prospects in Canine Cryptorchidism.

Sex Dev

November 2024

Department of Ribonucleoprotein Biochemistry, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland.

Background: Canine cryptorchidism, manifested by an abnormal testicular position, poses significant health risks and reproductive challenges in affected males. Despite a high prevalence, estimated at up to 10% in the canine population, a comprehensive understanding of its pathogenesis remains elusive. Studies in human cryptorchids and knockout mice have identified key factors involved in testicular descent, including INSL3, RXFP2, and AR.

View Article and Find Full Text PDF

Want 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!