Maintenance of human chromosome epigenetic states within a rodent cell has been demonstrated using human-rodent somatic cell hybrids (SCH), including the developmental status of globin gene expression, the active or inactive state of X chromosomes, and for genomic imprinting. We have now used a pig-rodent SCH panel [Yerle M, et al. (1996) Cytogenet Cell Genet. 73: 194-202] to assess imprinted gene expression and DNA methylation of candidate imprinted loci. Furthermore, we are using SCH as a cellular model to explore genome editing of pig chromosomes. The SCH lines by cytogenetic analysis contain on average 5-7 pig chromosomes, for this work including Sus scrofa chromosome 1 (SSC1) or SSC9. Using FISH with a whole SSC1 paint probe and with a specific Snord116 gene locus probe, we confirmed that five SCH have a single SSC1q18 region [the location of the Prader-Willi syndrome (PWS)-orthologous imprinted locus]. Gene expression analysis showed that the PWS-orthologous genes Snurf-Snrpn, Snord116, Snord107 and Magel2, as well as the syntenic Plagl1 gene, are differentially expressed in the SCH lines, consistent with an imprinted pattern of monoallelic expression. Using the methylation-sensitive restriction enzyme HhaI followed by PCR, the Snurf-Snrpn promoter was unmethylated in three SCH and methylated in two SCH, correlating with gene expression and enabling assignment of paternal or maternal origin of the pig SSC1. Similarly, we are currently analyzing SSC9 candidate imprinted genes. Transfection of SCH lines with vectors encoding transcription activator-like effector nucleases (TALENs) or the CRISPR (clustered, regularly interspaced, short, palindromic repeats)/Cas9 ribonucleoprotein system designed to target sites in the PWS-orthologous domain resulted in successful induction of double-strand breaks and repair by non-homologous end joining to generate deletions ranging from 2.05 kb to ≥1.2 Mb. Levels of genome editing by both designer nucleases were greater on the transcriptionally active, paternal allele than on the silent, maternal allele, with only some CRISPR gRNA pairs functional for the latter. In conclusion, SCH are a valuable resource for imprinting assays of candidate genes in the pig. Further, SCH provide a powerful cell model to test efficacy and mechanisms of genome editing of pig chromosomes by designer nucleases. Supported by NIH, FPWR, PWSA and the Storr Family Foundation.