scholarly journals Large-scale pedigree analysis leads to evidence for founder effects of hypertrophic cardiomyopathy in rhesus macaques (Macaca mulatta )

2014 ◽  
Vol 43 (4) ◽  
pp. 288-291 ◽  
Author(s):  
Sree Kanthaswamy ◽  
Rachel Reader ◽  
Ross Tarara ◽  
Karen Oslund ◽  
Mark Allen ◽  
...  
2021 ◽  
Vol 8 ◽  
Author(s):  
Yu Ueda ◽  
Samantha Kovacs ◽  
Rachel Reader ◽  
Jeffrey A. Roberts ◽  
Joshua A. Stern

In a colony of rhesus macaques at California National Primate Research Center (CNPRC), naturally occurring hypertrophic cardiomyopathy (HCM) classified by left ventricular hypertrophy without obvious underlying diseases has been identified during necropsy over the last two decades. A preliminary pedigree analysis suggested a strong genetic predisposition of this disease with a founder effect. However, the mode of inheritance was undetermined due to insufficient pedigree data. Since 2015, antemortem examination using echocardiographic examination as well as other cardiovascular analyses have been performed on large numbers of rhesus macaques at the colony. Based on antemortem examination, HCM was diagnosed in additional 65 rhesus macaques. Using HCM cases diagnosed based on antemortem and postmortem examinations, the heritability (h2) was estimated to determine the degree of genetic and environmental contributions to the development of HCM in rhesus macaques at the CNPRC. The calculated mean and median heritability (h2) of HCM in this colony of rhesus macaques were 0.5 and 0.51 (95% confidence interval; 0.14–0.82), respectively. This suggests genetics influence development of HCM in the colony of rhesus macaques. However, post-translational modifications and environmental factors are also likely to contribute the variability of phenotypic expression. Based on the pedigree analysis, an autosomal recessive trait was suspected, but an autosomal dominant mode of inheritance with incomplete penetrance was also possible. Further investigation with more data from siblings, offspring, and parents of HCM-affected rhesus macaques are warranted. Importantly, the findings of the present study support conducting genetic investigations such as whole genome sequencing to identify the causative variants of inherited HCM in rhesus macaques.


Author(s):  
Amber R Williams ◽  
Yu Ueda ◽  
Joshua A Stern ◽  
Kari L Christe

Vertebral heart scoring (VHS) is a semiquantitative method to assess the presence and severity of cardiomegaly by usingthoracic radiographs. VHS in rhesus macaques (Macaca mulatta) has not been validated or used routinely in the clinical orresearch setting. We hypothesized that rhesus macaques with cardiac disease diagnosed by using echocardiography wouldhave higher VHS than animals without cardiac disease. A total of 150 rhesus macaques were enrolled in this study. All animalsunderwent echocardiography and thoracic radiography (right lateral [RL], dorsoventral [DV], and ventrodorsal [VD] views).According to echocardiography, 121 rhesus macaques had no cardiac disease and were used to establish reference intervalsfor VHS. The remaining 29 macaques had hypertrophic cardiomyopathy (n = 20) or other cardiac disease (n = 9). Resultsshowed that VHS of RL and VD views were significantly higher in macaques with any of the identified cardiac diseases andin the cardiac disease group that excluded hypertrophic cardiomyopathy. VHS of animals with HCM was not significantlydifferent than that of control animals. In the RL view, VHS was moderately accurate for predicting the presence of cardiacdisease, with an AUC of 0.71 and an optimal cut-off value of 10.25 (sensitivity: 62%, specificity: 77%). In the VD view, VHSwas a mildly accurate test for cardiac disease, with an AUC of 0.654 and an optimal cut-off value of 10.65 (sensitivity, 66%;specificity, 63%). Study results indicated that VHS could be a useful screening tool for clinically identifying rhesus macaqueswith cardiac disease. However, VHS is unlikely to replace echocardiographic examination for determining the presence, type,and severity of cardiac disease in this species.


Meta Gene ◽  
2021 ◽  
pp. 100891
Author(s):  
Sanjoy Kumar Chatterjee ◽  
Suniti Yadav ◽  
Kallur Nava Saraswathy ◽  
Prakash Ranjan Mondal

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashwani Kesarwani ◽  
Parul Sahu ◽  
Kshama Jain ◽  
Prakriti Sinha ◽  
K. Varsha Mohan ◽  
...  

AbstractDue to the limited utility of Bacillus Calmette–Guérin (BCG), the only approved vaccine available for tuberculosis, there is a need to develop a more effective and safe vaccine. We evaluated the safety and efficacy of a dry powder aerosol (DPA) formulation of BCG encapsulated alginate particle (BEAP) and the conventional intradermal BCG immunization in infant rhesus macaques (Macaca mulatta). The infant macaques were immunized intratracheally with DPA of BEAP into the lungs. Animals were monitored for their growth, behaviour, any adverse and allergic response. The protective efficacy of BEAP was estimated by the ex-vivo H37Rv infection method. Post-immunization with BEAP, granulocytes count, weight gain, chest radiography, levels of liver secreted enzymes, cytokines associated with inflammation like TNF and IL-6 established that BEAP is non-toxic and it does not elicit an allergic response. The T cells isolated from BEAP immunized animals’ blood, upon stimulation with M.tb antigen, secreted high levels of IFN-γ, TNF, IL-6 and IL-2. The activated T cells from BEAP group, when co-cultured with M.tb infected macrophages, eliminated largest number of infected macrophages compared to the BCG and control group. This study suggests the safety and efficacy of BEAP in Non-human primate model.


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