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Animal Models

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Infant Isoflurane Exposure Affects Social Behaviours, but Does Not Impair Specific Cognitive Domains in Juvenile Non-Human Primates

Neudecker et al., British Journal of Anaesthesia. 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 et al., Hepatology. 2020.

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 (R24OD017870) and NIDDK.

Intra-Strain Genetic Variation of Platyfish (Xiphophorus maculatus) Strains Determines Tumorigenic Trajectory

Lu et al., Frontiers in Genetics . 2020.

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 (R24OD011120), NCI, and NIGMS.

Induction and Characterization of Pancreatic Cancer in a Transgenic Pig Model

Boas et al., PLOS One. 2020.

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 for 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 (U42OD011140) and NCI.