SCID Pig Model Development
The Tuggle lab at Iowa State is home to a line of Severe Combined Immunodeficient (SCID) pigs, which were serendipitously discovered in 2011 and further characterized in 2015. These pigs lack an adaptive immune system due to natural mutations in the Artemis gene. Given the lack of an immune system, these animals can be transplanted with human tissues and cells and used as a model for therapeutic testing.
The promise of stem-cell based therapies is not being fully realized due to a lack of appropriate preclinical animal models. Consequently, there remains a critical need to develop animal models that better translate results from preclinical research trials to the patient. The ISU SCID pig line is a model that is being developed to address this problem. The pig is known to be an excellent model for human biology due to similarities in size, physiology, and genetic code. This SCID model has been successfully engrafted with multiple cancer cell lines (including melanoma and ovarian), human skin, as well as human immune cells.
Our long-term goal is to create validated SCID models for broad use in preclinical testing of such stem-cell based therapies.
- Validate SCID pig models for preclinical testing of cell and tissue xenografts
- Optimize humanization approaches
- Establish second-generation SCID pig model management protocols at multiple biocontainment facilities
- Development and characterization of ART-/- IL2Rg-/Y SCID pigs and engraftment of human immune cells (2020)
- Human skin engraftment in ART-/- SCID (2020)
- Ovarian tumor development in ART-/- SCID pigs (2019)
- Biocontainment facilities for SCID pigs (2018)
- Bone marrow transplantation in ART-/- SCID pigs (2017)
- Characterization of NK cells in ART-/- SCID pigs (2016)
- Characterization of ART-/- SCID pigs (2015)
Functional Annotation of Animal Genomes (FAANG)
FAANG is an internationally collective project to understand and identify all functional elements in animal genomes. Our lab's contribution to FAANG is characterizing and annotating the porcine genome. Created resources will be critical tools for both agricultural, as well as biomedical, research.
- Continue functional annotation of adult porcine tissues
- Create functional annotation of tissues during fetal development
- Identify functional components of the immune system
- Integration of all collected data to understand the function of genome regions across biological states
- Reference transcriptomes of porcine peripheral immune cells created through bulk and single-cell RNA sequencing (BioRxiv, 2021)
- Comprehensive annotation of regulatory elements in the chicken, pig, and cattle genomes (2021)
- Comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues (2020)
- An improved pig reference genome sequence to enable pig genetics and genomics (2020)
- Changes in histone modifications in porcine alveolar macrophages after PAMP stimulation (2020)
- Annotation using Iso-Seq and RNA-Seq (2019)
Pig Immuno Genetics and Genomics in Iowa (PIGGI)
The PIGGI project encompasses aspects from both the SCID and FAANG projects taking place within Iowa. These projects focus specifically on characterizing the genetics and genomics of the porcine immune system.
- Differential induction of innate memory in porcine monocytes by beta-glucan or bacillus Calmette-Guerin (2020)
- Differences in acute systemic inflammatory processes with lipopolysaccharide in pigs divergently selected for residual feed intake (2019)