Fat rats at an Indian research institute may carry undiscovered obesity genes. Credit: Courtesy: National Institute of Nutrition

The world's fattest rats are the focus of a new joint project for scientists from India and the US. The researchers hope to identify and clone the genes responsible for the 'sumo' rats that weigh in at about 1.4 kilograms (3.1 pounds), about four times the standard weight for a rat.

“If, as we believe, this is a new obesity gene, it could have major implications,” says Nappan Veettil Giridharan, deputy director of India's National Institute of Nutrition (NIN) in Hyderabad. The NIN maintains a colony of about 400 sumo rats in their twenty-first generation. Giridharan says all evidence indicates that the genes may differ from all obese rat models currently available.

Like other rodent models, the sumo rats serve as good paradigms for human disorders such as diabetes and infertility. But unlike the other models, these rats also develop cataracts and tumors, and their infertility is fully reversible with simple measures such as diet restriction. The rats also have kinky tails, not seen in any other obese models.

From day 35 on, the rats rapidly gain weight and their body shape gradually becomes rotund. Too fat to move, they lie supine with their heads close to the food pellets. They also show signs of rapid aging and die in about 18 months, compared with the normal three years, Giridharan says.

To map the mutation, Giridharan and his colleagues plan to cross the Indian rat with unrelated strains such as the Brown Norway and Fischer-344 strains. Genetic analysis on the resulting progeny will then help localize the mutation and ultimately clone it. DNA analysis will be carried out by the US collaborators, led by Jeffrey Friedman, at Rockefeller University in New York.

We are ready to start the project right away and hopefully clone the gene in two years. Jeffrey Friedman,, Rockefeller University

In 1994, Friedman and his colleagues cloned the obese gene and, in 1995, identified its product, leptin. Friedman showed that overweight mice with defective ob genes—and who cannot make leptin—respond to injections of leptin by losing up to 30% of their body weight in two weeks.

The $500,000 cost of the project is to be shared by the US National Institutes of Health and the Indian Council of Medical Research (ICMR).

“We are ready to start the project right away and hopefully clone the gene in two years,” says Friedman. The ICMR is planning another large study to use the NIN rat to screen for potential obesity and diabetes drugs.