Genetic ‘dial’ to control body size in pigs identified.
Transplants save thousands of lives every year, however, there is an acute shortage of human donors. This shortage has led to attempts to develop animal organs that can be transplanted into humans or xenotransplantation. Therefore genetic modification is highly desirable to match organs between different species, particularly where organs are genetically similarly but outmatched in size. Now, a study from researchers at North Carolina State University demonstrates a connection between the expression of the HMGA2 gene and body size in pigs. The team state their work further demonstrates the gene’s importance in body and organ size regulation across mammalian species, and provides a target for gene modification. The opensource study is published in the Proceedings of the National Academy of Sciences.
Previous studies show that HMGA2 is a gene that controls the total number of cells that an animal has. The gene is only active during fetal development, and programs the number of cells that the animal will be able to generate. When the animal is born, it will only be able to grow to the size dictated by the number of cells HMGA2 says that it can produce. Researchers have studied the HMGA2 analogue in mice, which have two different genes (HMGA2 and HMGA1) involved in body size and body mass index determination. Pigs and humans share the HMGA2 gene responsible for growth regulation in their species. The current study investigates body size in pigs which express both copies of the gene, one copy, or neither copy.
The current study generates male and female fetal fibroblasts cell lines as somatic cell nuclear transfer donors to investigate the effect of disruption of both copies of the HMGA2 gene on fetal and adult growth in pigs. Results show the amount of the gene expressed is proportional to the size of the animal. Data findings show that when both copies are expressed the pig was ‘normal’ sized, and when one copy is expressed the pig is roughly 25% smaller than normal, and if neither copy is expressed the pig is 75% smaller.
Results show that the deletion of HMGA2 affects the resources that the pig fetuses received in utero; in litters containing fetuses with both copies of the gene deleted and fetuses with one or more copy of the gene expressed, the fetuses with both copies deleted did not survive the pregnancy. Data findings show that if the litter only contained fetuses with both copies deleted, the fetuses survived and developed normally. The team state that animals grow and develop normally, although the boars with both copies of the gene deleted were sterile. They go on to add that overall, it seems that controlling the expression of HMGA2 is like using a dial to control body size.
The team surmise their data identifies the gene responsible for body-size reduction of over 80%, fetal competition, and cryptochidism in pigs. For the future, the researchers state that this opens up the possibility of regulating size in multiple mammalian species and the size reduction of organs to be used in xenotransplantation, allowing a better match between the organ size of donor and recipient and avoiding some of the issues that have been recently identified due to organ overgrowth after transplantation.
Source: North Carolina State University