Grantee Publications

Last Updated: January 8, 2021

 

Responses to Acute Infection with SARS-CoV-2 in the Lungs of Rhesus Macaques, Baboons and Marmosets
Singh, Dhiraj K. et al., Nature Microbiology, 18 December 2020 
https://www.nature.com/articles/s41564-020-00841-4
Investigators compared acute SARS-CoV-2 infection in young and old rhesus macaques and baboons. Macaques had clinical signs of viral infection, mild to moderate pneumonitis and extra-pulmonary pathologies; both age groups recovered within two weeks. Baboons had prolonged viral RNA shedding and more lung inflammation compared with macaques; inflammation in bronchoalveolar lavage was increased in old versus young baboons. Macaques developed T-cell memory responses and bystander cytokine production. Old macaques had lower titers of SARS-CoV-2-specific IgG antibody levels compared with young macaques. The results indicate macaques and baboons experience acute respiratory distress that recapitulates the progression of COVID-19 in humans. 
Supported by ORIP (P51OD111033 and U42OD010442) and NIAID.


Germline Transmission of Donor, Maternal and Paternal mtDNA in Primates
Ma, Hong et al, 2020;
https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deaa308/6025644#218455297 
Mitochondrial gene mutations contribute to incurable human disorders. The possibility of using mitochondrial replacement therapy (MRT) to prevent transmission of pathogenic mitochondrial (mt)DNA was explored in rhesus macaques. Development of spindle MRT transfer in oocytes in 5 female rhesus macaques resulted in healthy and fertile offspring.  These results demonstrate that MRT is compatible with normal postnatal development including overall health and reproductive fitness in nonhuman primates with no detected adverse effects. Additional research is needed to more fully explore the use of MRT to prevent disorders as this study had a limited number of animals with only one female offspring. 
Supported by ORIP (P51OD0092) and NIA.


Infant Isoflurane Exposure Affects Social Behaviours, but Does Not Impair Specific Cognitive Domains in Juvenile Non-human Primates
Neudecker, Viola et al., British Journal of Anaesthesia 14 November 2020
https://www.sciencedirect.com/science/article/pii/S0007091220308503
Researchers investigated the impact of extended (5 hours) isoflurane anesthetic exposure (1-3 exposures) of rhesus macaque (RM) infants of both sexes on cognitive testing and behavioral assessments. Cognitive function did not differ among groups; however, compared to controls, RMs exposed three times during infancy exhibited less close social behavior. One isoflurane exposure resulted in increased anxiety-related behaviors and more inhibition towards novel objects. These findings are consistent with behavioral alterations observed in social settings of human clinical studies. 
Supported by ORIP (P51OD011092). 


Estrogen Acts Through Estrogen Receptor 2b to Regulate Hepatobiliary Fate During Vertebrate Development
Chaturantabut, Saireudee et al. Hepatology. 2020 Nov;72(5):1786-1799
https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.31184
During liver development, bipotent progenitor cells differentiate into hepatocytes and biliary epithelial cells to ensure a functional liver. The developmental cues controlling the differentiation of committed progenitors into these cell types are not completely understood. These authors report an essential role for estrogenic regulation in vertebrate liver development to affect hepatobiliary fate decisions. The studies identify17β-estradiol (E2), nuclear estrogen receptor 2b (esr2b), and downstream bone morphogenetic protein (BMP) activity as important regulators of hepatobiliary fate decisions during vertebrate liver development. These results have significant implications for liver development in infants exposed to abnormal estrogen levels or estrogenic compounds during pregnancy.
Supported by ORIP (R24 OD017870), NIDDK.

Intra-Strain Genetic Variation of Platyfish (Xiphophorus maculatus) Strains Determines Tumorigenic Trajectory
Lu, Yuan et al., Frontiers in Genetics 2020 Oct 6;11:562594
https://www.frontiersin.org/articles/10.3389/fgene.2020.562594/full
Xiphophorus interspecies hybrids represent a valuable model system to study heritable tumorigenesis. Although the ancestors of the two X. maculatus parental lines, Jp163 A and Jp163 B, were siblings produced by the same mother, backcross interspecies hybrid progeny between X. hellerii and X. maculatus Jp163 A develop spontaneous melanoma initiating at the dorsal fin due to a regulator encoded by the X. maculatus genome; the backcross hybrid progeny with X. hellerii or X. couchianus and Jp163 B exhibit melanoma on their flanks. Comparative genomic analyses revealed genetic differences are associated with pathways highlighting fundamental cellular functions. Disruption of these baselines may give rise to spontaneous or inducible tumorigenesis.
Supported by ORIP (R24 OD-011120), NCI, NIGMS.

Induction and Characterization of Pancreatic Cancer in a Transgenic Pig Model
Boas, F. Edward et al., PLoS One. 2020 Sep 21;15(9):e0239391
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239391
Preclinical testing of new therapies for pancreatic cancer has been challenging due to lack of a suitable large animal model. Pigs, however, have similar physiology and immune response to humans. Boas et al report the development of a porcine model of pancreatic cancer.  H&E and immunohistochemical stains revealed undifferentiated carcinomas, like those of human pancreatobiliary systems. In several pigs, angiographies revealed that the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. In summary, pancreatic cancer can be induced in a transgenic pig, and intra-arterial procedures using catheters designed for human interventions were feasible in this model. 
Supported by ORIP (U42 OD011140), NCI.