Cytokines in abdominal aortic aneurysm: master regulators with clinical application

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokine

On the way from SARS-CoV-sensitive mice to murine COVID-19 model

The coronavirus disease 2019 (COVID-19) is a master killer which appeared suddenly and which has already claimed more than 200,000 human lives. In this situation, laboratories are in urgent need for a COVID-19 murine model to search for effective antiviral compounds. Here we propose a novel strategy for the development of mice that can be inoculated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the COVID-19 causative agen

The tissue distribution of SARS-CoV-2 in transgenic mice with inducible ubiquitous expression of hACE2

The novel coronavirus disease COVID-19 has become one of the most socially significant infections. One of the main models for COVID-19 pathogenesis study and anti-COVID-19 drug development is laboratory animals sensitive to the virus. Herein, we report SARSCoV- 2 infection in novel transgenic mice conditionally expressing human ACE2 (hACE2), with a focus on viral distribution after intranasal inoculation. Transgenic mice carrying hACE2 under the floxed STOP cassette [(hACE2-LoxP(STOP)] were mated with two types of Cre-ERT2 strains (UBC-Cre and Rosa-Cre

Genetically modified animals for use in bio‑pharmacology: from research to production

In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiate

Retinal abnormalities in transgenic mice overexpressing aberrant human FUS[1-359] gene

The aim of this work was to assess the structural and functional state of the retina in a murine model of ALS caused by overexpression of the aberrant FUS protein [1-359]. The retinal examination was carried out on 12 transgenic and 13 wild-type mice of 2.5-3 months of age. The study revealed not statistically significant higher level of ophthalmoscopic violations in FUS[1-359] mic

A bioisostere of Dimebon/Latrepirdine delays the onset and slows the progression of pathology in FUS transgenic mice

Avtors developed a CatWalk analysis protocol that allows detection of gait changes in FUS transgenic mice and the effect of DF402 on their gait already at early pre-symptomatic stage. At this stage, a limited number of genes significantly change expression in transgenic mice and for 60% of these genes, DF402 treatment causes the reversion of the expression patter

Genetic markers in sheep meat breeding

Cattle breeding, including sheep farming, is an important sector of agriculture. Increasing productivity and improving meat quality are considered today as the priorities in the industry. Significant advances have been achieved in sheep breeding through the use of genetics. The commonplace of all selection programs is using manufacturers selected on the basis of the quality of the offspring, relatives or ancestors. At the same time, using the achievements of molecular genetics can lead breeding to a new methodological level. The problem of finding reliable communication between productivity features and genetic markers has not yet been solved, because productivity is a set of features (unlike, for example, monogenic diseases) and its expression depends on the balance between various physiological functions. By contrast, imbalance may cause reduced productivity as a whole even if there is a positive role of prevailing element. Selection on the basis of genetic markers of productivity aims to work with animals with high genetic potential for weight gain and meat quality. This review considers promising genes – potential markers of productivity in sheep farming, such as growth hormone gene, callipyge, calpain and calpastatin, which have promise as genetic markers for sheep selection. However, it should be stated that in spite of numerous reports about potential genetic markers of productivity there is still no data about the influence of molecular genetic methods on improving the economic performance of sheep selection

Retinal damage in amyotrophic lateral sclerosis: underlying mechanisms

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in a gradual loss of motor neuron function. Although ophthalmic complaints are not presently considered a classic symptom of ALS, retinal changes such as thinning, axonal degeneration and inclusion bodies have been found in many patient

CRISPR/Cas9-generated mouse model with humanizing single-base substitution in the Gnao1 for safety studies of RNA therapeutics

The development of personalized medicine for genetic diseases requires preclinical testing in the appropriate animal models. GNAO1 encephalopathy is a severe neurodevelopmental disorder caused by heterozygous de novo mutations in the GNAO1 gene. GNAO1 c.607 G>A is one of the most common pathogenic variants, and the mutant protein Gαo-G203R likely adversely affects neuronal signaling. As an innovative approach, sequence-specific RNA-based therapeutics such as antisense oligonucleotides or effectors of RNA interference are potentially applicable for selective suppression of the mutant GNAO1 transcript. While in vitro validation can be performed in patient-derived cells, a humanized mouse model to rule out the safety of RNA therapeutics is currently lacking. In the present work, we employed CRISPR/Cas9 technology to introduce a single-base substitution into exon 6 of the Gnao1 to replace the murine Gly203-coding triplet (GGG) with the codon used in the human gene (GGA). We verified that genome-editing did not interfere with the Gnao1 mRNA or Gαo protein synthesis and did not alter localization of the protein in the brain structures. The analysis of blastocysts revealed the off-target activity of the CRISPR/Cas9 complexes; however, no modifications of the predicted off-target sites were detected in the founder mouse. Histological staining confirmed the absence of abnormal changes in the brain of genome-edited mice. The created mouse model with the “humanized” fragment of the endogenous Gnao1 is suitable to rule out unintended targeting of the wild-type allele by RNA therapeutics directed at lowering GNAO1 c.607 G>A transcripts

Association between HSPA8 Gene Variants and Ischemic Stroke: A Pilot Study Providing Additional Evidence for the Role of Heat Shock Proteins in Disease Pathogenesis

HSPA8 is involved in many stroke-associated cellular processes, playing a pivotal role in the protein quality control system. Here we report the results of the pilot study aimed at determining whether HSPA8 SNPs are linked to the risk of ischemic strok