'Trimming the fat' with CRISPR

Around 20 million years ago, for unknown reasons, wild pigs lost an important metabolic gene known as uncoupling protein 1 (UCP1). In most mammals this gene plays a major role in generating body heat for thermoregulation, and lack of UCP1 has led to some unusual physiological traits in all modern domestic and wild pig species¹. Unlike most mammals, pigs generate heat in response to cold temperatures primarily by shivering, instead of by increasing metabolic rate. In fact, pigs seem to entirely lack brown adipose tissue, the type of fat specialized in thermoregulation. As a consequence, piglets are exceptionally susceptible to cold-related death, and adult pigs tend to accumulate excess fat as a result of their unusual metabolic traits. From an agricultural perspective, there are significant economic costs due to neonatal mortality, heating animal barns, and feed costs associated with excess fat production. Piglet death also represents an obvious animal welfare issue.

A team of scientists in Beijing have addressed these issues by using a CRISPR/Cas9-based approach². They generated knockin pigs carrying the mouse UCP1 gene under the control of an adipose-specific promoter, which resulted in functional UCP1 activity in white adipose tissue. The genetically-modified pigs have measurably better thermoregulation and significantly lower body fat. These pigs can now regulate their body temperature by burning fat, like most mammals, leading to smaller fat deposits than in normal pigs. Agricultural experts and scientists expect that correcting pig UCP1 deficiency will save pig farmers millions of dollars and also significantly increase animal welfare.

Cyagen Biosciences can help you harness the experimental power of animal models in your own research. We provide custom mouse and rat models, including transgenics, knockouts and knockins, CRISPR/Cas9 and TALEN genome editing, as well as custom virus packaging, stem cells, and cell culture reagents. Our VectorBuilder platform allows you to design and order custom DNA constructs specific to your experimental needs. Choose from lentiviruses, adenovirus, AAV, shRNA expression vectors, CRISPR/Cas9 vectors, and more!

References

1. Berg F, Gustafson U, Andersson L. The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets. PLoS Genet. 2006 Aug 18;2(8):e129.
2. Zheng Q, Lin J, Huang J, et al. Reconstitution of UCP1 using CRISPR/Cas9 in the white adipose tissue of pigs decreases fat deposition and improves thermogenic capacity. PNAS 2017 ; epub ahead of print October 23, 2017