117 Improved Growth Performance in the F1 Heterozygous Generation of an SSTR2 Knockout Model in Swine

Abstract Targeted genetic alteration provides opportunities for rapid genetic improvement in resilience, welfare and production traits. Somatostatin (SST) acts via negative feedback to regulate growth hormone (GH) activity by antagonizing GH releasing hormone via SST receptors (SSTR) located in the anterior pituitary. Our objective was to reduce the negative effect of SST in the anterior pituitary on protein accretion by reducing the number of functional copies of SSTR2 using the CRISPR/Cas9 system. We hypothesized that a reduction or elimination of SSTR2 would lead to improved growth performance. To test this hypothesis, three commercial gilts were bred with semen from a founder boar in a compound heterozygous state at the SSTR2 locus with a 1bp deletion in one allele resulting in a premature stop codon and a 3bp deletion in the other allele resulting in the loss of a single amino acid predicted to remain functional after translation. Three litters of F1 offspring were produced (n = 46) and all piglets were confirmed to be heterozygous at the SSTR2 locus with one wild type allele and the other possessing either the 1bp deletion (n = 22) or the 3bp (n = 2 4) deletion. No differences (P > 0.43; n=46) in body weight (1.27±0.03 kg) across comparisons were observed at birth. At weaning (n = 36), males (6.19±0.20 kg) were heavier (P = 0.007) than females (5.41±0.19 kg), and piglets possessing a 1bp deletion (6.00±0.20 kg) were numerically heavier (P = 0.14) than 3bp deletion pigs (5.59±0.18 kg). This observation was more pronounced in males at weaning, where the males with the 1bp deletion were 13% heavier (P = 0.058) than those with the 3bp deletion. These data suggest that altering SSTR2 may be a viable genetic advancement strategy to improve growth performance in pigs. This project was supported by the Lloyd L. Anderson Professorship in Physiology at Iowa State University.