Nile rat genome may clarify type 2 diabetes in humans

Nile rat genome may clarify type 2 diabetes in humans

Researchers have assembled the first Nile rat reference genome.

The reference genome is a kind of genetic model of this species which can be used for laboratory and clinical studies.

The hope, according to researcher Huishi Toh of the University of California, Santa Barbara, is that it will be useful to those studying type 2 diabetes and the neurological disorders associated with a disturbed diurnal rhythm.

The Nile rat is prone to diet-induced diabetes and exhibits a clear diurnal pattern, unusual in rodents.

“It was a risk, and it took a long time,” says the study’s lead author, Toh, an assistant project scientist in the lab of cell biologist Dennis Clegg. “But when you’re assembling a new genome, you have to be aware of various sequencing errors.”

Model organisms are among our best aids in understanding some of our most complex diseases and are often chosen for, among other things, their similarity to humans in a physical or genetic way. This is the case of the house mouse and brown rat, which are used to study the underlying genetics of certain human diseases.

But this is not a unique situation, especially in the case of type 2 diabetes, which today affects more than 35 million people in the United States. While researchers have used common laboratory mice and rats to improve our understanding of the disease, tracing the development of diet-induced diabetes and its complications in the most typical rodent models has not been very rewarding. .

“A major problem in modeling type 2 diabetes is that laboratory rats and mice are not particularly susceptible to diet-induced diabetes,” says Toh. “Obesity-induced mice are actually models of pre-diabetes, and genetic or chemical manipulations are often required to induce these conventional rodents to develop diabetes and its complications, thus not mimicking the natural progression of diabetes. type 2 in humans.

Over the past two decades, however, the Nile rat has emerged as a potential model for type 2 diabetes. Native to the grasslands of sub-Saharan Africa, these rodents live on a high fiber, low carbohydrate diet, unlike their more urban cousins ​​who may have already adapted to a more humane, high-carb diet.

It turns out that the lab food was high in calories for the Nile rats and they would spontaneously develop diet-induced diabetes, like humans.

Previously, the Thomson lab demonstrated that the Nile rat could develop diabetic retinopathy with key features of vision loss – similar to those in humans – and lacking in other rodent models, solidifying the Nile rat as a model of well-developed type 2 diabetes.

What was missing was a reference genome, a genetic sequence that represents the animal in general and that can serve as a touchstone or starting point in the search for genetic variations that may indicate susceptibility to certain diseases and others. gene-related conditions.

In partnership with the Vertebrate Genome Project, the Morgridge Institute for Research and the University of Southern California, the researchers assembled a “highly complete and highly contiguous” genome.

Among the things they noticed when comparing the Nile rat genome to the lab mouse genome was that the Nile rat had fewer copies of a gene that codes for the carbohydrate processing enzyme called amylase, possibly reflecting the lack of adaptation of high-starch diets. .

“We think the Nile rat is not adapted to eat carbohydrate-rich foods, which makes sense because they normally eat grass in Africa,” Toh says. “I think that’s why they’re so susceptible to diabetes.”

Conversely, laboratory mice – having lived near and around humans – had more copies of this gene, a sign of evolutionary adaptation to their environment.

In fact, says Toh, one of the benefits of having a reference genome is that it becomes possible to witness the genetic consequences of environmental impact.

“Currently, we are using this reference genome to study transcriptomic changes relevant to the initial development of diet-induced diabetes,” she says, “and we hope to eventually examine epigenetics as well.”

The study appears in BMC Biology.

The Garland Initiative for Vision, funded by the William K. Bowes Jr. Foundation, funded the work.

Source: University of Santa Barbara

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