scholarly journals The impact of genetic background and sex on the phenotype of IL-23 induced murine arthritis

2021 ◽  
Author(s):  
Emma Haley ◽  
Mederbek Matmusaev ◽  
Imtiyaz N. Hossain ◽  
Sean Davin ◽  
Tammy M. Martin ◽  
...  

AbstractBackgroundOverexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated.MethodsWe compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8-12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA.FindingsMale B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight.ConclusionsSystemic IL-23 overexpression results in spondyloarthritis-like disease in B10.RIII mice. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests organ-specific genetic control mechanisms of IL-23 driven inflammation. Discrepancies regarding the phenotype of IL-23 induced disease in different labs and the sexual dimorphism observed in this study warrant further exploration.

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0247149
Author(s):  
Emma K. Haley ◽  
Mederbek Matmusaev ◽  
Imtiyaz N. Hossain ◽  
Sean Davin ◽  
Tammy M. Martin ◽  
...  

Background Overexpression of IL-23 in adult mice by means of hydrodynamic tail vein injection of IL-23 minicircles has been reported to result in spondyloarthritis-like disease. The impact of genetic background and sex on the disease phenotype in this model has not been investigated. Methods We compared male B10.RIII mice with male C57BL/6 mice, and male with female B10.RIII mice after hydrodynamic injection of IL-23 enhanced episomal vector (EEV) at 8–12 weeks of age. We monitored clinical arthritis scores, paw swelling, and body weight. Animals were euthanized after two weeks and tissues were harvested for histology, flow cytometry and gene expression analysis. Serum cytokine levels were determined by ELISA. Findings Male B10.RIII mice developed arthritis in the forepaws and feet within 6 days after IL-23 EEV injection; they also exhibited psoriasis-like skin disease, colitis, weight loss, and osteopenia. In contrast to previous reports, we did not observe spondylitis or uveitis. Male C57BL/6 mice injected with IL-23 EEV had serum IL-23 levels comparable with B10.RIII mice and developed skin inflammation, colitis, weight loss, and osteopenia but failed to develop arthritis. Female B10.RIII mice had more severe arthritis than male B10.RIII mice but did not lose weight. Conclusions The phenotype of IL-23 induced disease in mice is controlled by genetic background and sex of the animals. The development of extra-articular manifestations but absence of arthritis in C57BL/6 mice suggests that organ-specificity of IL-23 driven inflammation is genetically determined. The mechanisms behind the strain-specific differences and the sexual dimorphism observed in this study may be relevant for human spondyloarthritis and warrant further exploration.


2019 ◽  
Vol 317 (5) ◽  
pp. F1201-F1210
Author(s):  
Leslie S. Gewin ◽  
Megan E. Summers ◽  
Julie W. Harral ◽  
Christa F. Gaskill ◽  
Stellor Nlandu Khodo ◽  
...  

Tuberous sclerosis complex 2 (TSC2), or tuberin, is a pivotal regulator of the mechanistic target of rapamycin signaling pathway that controls cell survival, proliferation, growth, and migration. Loss of Tsc2 function manifests in organ-specific consequences, the mechanisms of which remain incompletely understood. Recent single cell analysis of the kidney has identified ATP-binding cassette G2 (Abcg2) expression in renal proximal tubules of adult mice as well as a in a novel cell population. The impact in adult kidney of Tsc2 knockdown in the Abcg2-expressing lineage has not been evaluated. We engineered an inducible system in which expression of truncated Tsc2, lacking exons 36–37 with an intact 3′ region and polycystin 1, is driven by Abcg2. Here, we demonstrate that selective expression of Tsc2fl36–37 in the Abcg2pos lineage drives recombination in proximal tubule epithelial and rare perivascular mesenchymal cells, which results in progressive proximal tubule injury, impaired kidney function, formation of cystic lesions, and fibrosis in adult mice. These data illustrate the critical importance of Tsc2 function in the Abcg2-expressing proximal tubule epithelium and mesenchyme during the development of cystic lesions and remodeling of kidney parenchyma.


2016 ◽  
Vol 22 ◽  
pp. 145-146
Author(s):  
Tiffany Schwasinger-Schmidt ◽  
Georges Elhomsy ◽  
Fanglong Dong ◽  
Bobbie Paull-Forney

2004 ◽  
Author(s):  
Bruce Blaine ◽  
Jennifer McElroy ◽  
Hilary Vidair
Keyword(s):  

Obesity ◽  
2012 ◽  
Author(s):  
Melanie R. Jay ◽  
Colleen C. Gillespie ◽  
Sheira L. Schlair ◽  
Stella M. Savarimuthu ◽  
Scott E. Sherman ◽  
...  

2013 ◽  
Vol 16 (6) ◽  
pp. 336
Author(s):  
Marko Boban ◽  
Viktor Persic ◽  
Zeljko Jovanovic ◽  
Niksa Drinkovic ◽  
Milan Milosevic ◽  
...  

<p><b>Background:</b> Current knowledge on the pervasiveness of increased nutritional risk in cardiovascular diseases is limited. Our aim was to analyze the characteristics of nutritional risk screening in patients scheduled for rehabilitation after heart surgery. Prevalence and extent of nutritional risk were studied in connection with patients' characteristics and seasonal climate effects on weight loss dynamics.</p><p><b>Methods:</b> The cohort included 65 consecutive patients with an age range of 25-84 years, 2-6 months after surgical treatment for ischemic or valvular heart disease. Nutritional risk screening was appraised using a standardized NRS-2002 questionnaire. Groups were analyzed according to a timeline of rehabilitation according to the "cold" and "warm" seasons of the moderate Mediterranean climate in Opatija, Croatia.</p><p><b>Results:</b> Increased nutritional risk scores (NRS-2002) of >3 were found in 96% of studied patients. Mean NRS-2002 of patients was 5.0 � 1.0, with a percentage weight loss history of 11.7% � 2.2% (4.6-19.0). Risk was found to be more pronounced during the warmer season, with NRS-2002 scores of 5.3 � 0.7 versus 4.8 � 1.1 (<i>P</i> = 0.136) and greater loss of weight of 13.0% � 3.2% versus 10.6% � 3% (<i>P</i> = 0.005), respectively. Increased nutritional risk correlated significantly with creatinine concentrations (rho = 0.359; <i>P</i> = 0.034 versus 0.584; <i>P</i> = 0.001, respectively). Significant discordance in correlations was found between NRS-2002 and the decrease in left ventricle systolic function (rho correlation coefficient [rho-cc] = -0.428; <i>P</i> = 0.009), the increase in glucose concentrations (cc = 0.600; <i>P</i> < 0.001), and the decrease in erythrocyte counts (cc = -0.520; <i>P</i> = 0.001) during the colder season.</p><p><b>Conclusion:</b> Increased nutritional risk was found to be frequently expressed in the course of rehabilitation after heart surgery. Although seasonal climate effects influenced the weight loss dynamics, the impact on reproducibility of NRS-2002 was clinically less important. Further studies on the connection of nutritional risk with composited end points might offer improvements in overall quality of treatment.</p>


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 828-P
Author(s):  
MARCELA RODRIGUEZ FLORES ◽  
SYLVANA STEPHANO Z. ◽  
MARÍA RABASA ◽  
JUANA MONTOYA ◽  
CLAUDIA VELEZ ◽  
...  

2018 ◽  
Vol 1 (3) ◽  
pp. 176-181 ◽  
Author(s):  
E. Tettey

Under-fermentation of cocoa beans produces purple beans. The fermentation period is 6 to 7 days but some cocoa farmersunder-ferment their cocoa beans leading to the development of purple cocoa beans. This study determined the impact of insectinfestation on stored purple cocoa beans. Wet cocoa beans were fermented for 1, 2, 3, 4 and 5 days to produce the purple beans.Ephestia cautella and Tribolium castaneum, both singly and in combination, were introduced into the cocoa beans and storedfor different (30, 60, 90 and 120 days) period. Insect population, percentage weight loss and the contaminants produced bythese insects were determined. Cocoa beans infested with E. cautella alone had the highest population of 297.0 ± 22.7. Beansfermented for 3 days had the lowest insect population both singly and in combination after 120 days of storage. The highestpercentage weight loss was recorded in cocoa beans fermented for one day (10.1 ± 1.87%) and 4 days (10.1 ± 8.74%). T.castaneum did not cause much damage to the cocoa beans but E. cautella alone caused significant damage to stored cocoabeans. Insect infestation and poor fermentation contribute significantly to the reduction in quality of cocoa beans.


2019 ◽  
Vol 15 (3) ◽  
pp. 172-173 ◽  
Author(s):  
Valdemar Grill ◽  
Bjørn O. Åsvold

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than “classical” type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis has been challenged. Despite the absence of a genetic background that is exclusive to LADA, this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems as to therapy and follow-up perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA.


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