KRAS(G12D) and TP53(R167H) Cooperate to Induce Pancreatic Ductal Adenocarcinoma in Sus scrofa Pigs

Although survival has improved in recent years, the prognosis of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poor. Despite substantial differences in anatomy, physiology, genetics, and metabolism, the overwhelming majority of preclinical testing relies on transgenic mice. Hence, while mice have allowed for tremendous advances in cancer biology, they have been a poor predictor of drug performance/toxicity in the clinic. Given the greater similarity of sus scrofa pigs to humans, we engineered transgenic sus scrofa expressing a LSL-KRASG12D-TP53R167H cassette. By applying Adeno-Cre to pancreatic duct cells in vitro, cells self-immortalized and established tumors in immunocompromised mice. When Adeno-Cre was administered to the main pancreatic duct in vivo, pigs developed extensive PDAC at the injection site hallmarked by excessive proliferation and desmoplastic stroma. This serves as the first large animal model of pancreatic carcinogenesis, and may allow for insight into new avenues of translational research not before possible in rodents

Analyses of pig genomes provide insight into porcine demography and evolution

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model

A comparison of LH responses to intracerebroventricular, subcutaneous and intravenous administration of small doses of GnRH in cattle

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Bibliography: leaves 57-70.Not availabl

PA_Wild_boar_map

Information on the 49508 autosomal SNPs in .map file format corresponding to the genotypes in the PA_Wild_boar.ped file for use in PLINK softwar

README

Short explanation of file conten

PA_Wild_boar_info_micros

Wild boar sample information corresponding to PA_Wild_boar_micros and PA_Wild_boar_micros_structur

PA_Wild_boar_info_SNPs

Wild boar sample information corresponding to PA_Wild_boar_ped and PA_Wild_boar_SNP_structur

PA_Wild_boar_SNP_structure

STRUCTURE file with 91 wild boar SNP genotypes from Southern Balkan

PA_Wild_boar_micros_structure

STRUCTURE file of 555 Southern Balkan wild boar microsatellite genotype

PA_Wild_boar_ped

91 Southern Balkan wild boar genotypes in 49508 SNPs in .ped format for PLIN