Introducing the Göttingen Micropig

Göttingen Minipigs are a favorable non-rodent species for preclinical trials and translational research. One of their advantages over large pigs is their small size, making them easier to handle and reducing the dosage of test substances. Targeted knock-out of the growth hormone receptor gene (GHR-KO) is a biotechnological approach to further reduce the size of Göttingen Minipigs, thus generating “Göttingen Micropigs”. This approach was successfully performed and intensively investigated in regular-sized pigs with German Landrace (GL) genetic background to generate the (GL) GHR-KO pig, resembling characteristics of the human Laron syndrome such as low serum insulin-like growth factor 1 (IGF1), high but non-functional growth hormone (GH) levels, and postnatal growth retardation. Besides the reduction in size, no deleterious effects on the immune system and metabolism or limitations in the usage of this animal model for cardiovascular research were observed. A defined biallelic GHR-KO mutation has been introduced in Göttingen Minipig primary kidney cells, which were used for somatic cell nuclear transfer. Laparoscopic transfer of cloned embryos into wild-type GL recipient gilts resulted in the birth of GHR-KO Göttingen Micropig founder boars. Their serum IGF1 levels (23.1±4.6 mg/mL; n=7) were comparable to GL GHR-KO pigs (19.3±1.5 mg/mL; n=13) and markedly reduced compared to wild-type Göttingen Minipigs (289.0±18.2 mg/mL; n=5) and wild-type GL pigs (238.1±30.4 mg/mL; n=12). The Göttingen Micropig boars showed stagnating growth from an age of 7 months onwards, reaching 14.9 and 24.9 kg at 16 months while an average body weight of 34.26 kg is reported for wild-type Göttingen Minipig boars at that age. Sperm from Göttingen Micropig boars was used for insemination of wild-type Göttingen Minipig gilts at Ellegaard Göttingen Minipigs A/S, resulting in heterozygous GHR transgenic piglets. From those, a breeding herd of Göttingen Micropigs will be established and further characterized regarding their applicability for preclinical research.