Genetic ‘dial’ to control body size in pigs identified.

Organ 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 capable of being transplanted into humans, a technique known as xenotransplantation.  Therefore, genetic modification is highly desirable to match organs between different species, particularly where organs are genetically similar and 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 states 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 have shown HMGA2 is a gene controlling the total number of cells an animal has.  The gene is only active during fetal development and programs the number of cells the animal will ultimately 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 it can produce.  Researchers have studied the HMGA2 analog in mice, who have two different genes (HMGA2 and HMGA1) involved in body size and body mass index determination. The current study investigates body size in pigs, who share the HMGA2 gene with humans, expressing 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 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 the deletion of HMGA2 affects the resources the pig fetuses received in utero, and in litters containing fetuses with both copies of the gene deleted and fetuses with one or more copies of the gene expressed, the fetuses with both copies deleted did not survive the pregnancy.  Data findings show if the litter only contained fetuses with both copies deleted, the fetuses survived and developed normally.  The team states animals grow and develop normally, although the boars with both copies of the gene deleted were sterile. They go on to add overall, it appears controlling the expression of HMGA2 is like using a dial to control body size.

The team surmises their data identifies the gene responsible for the body-size reduction of over seventy-five percent, fetal competition, and cryptorchidism in pigs.  For the future, the researchers state 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.

Source: North Carolina State University

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