Question

We are interested in factors that contribute to obesity. The discovery of the hormone leptin suggests that appetite control is influenced by this compound. Biologists have identified a strain of mutant mice that become obese when offered free access to food. However, genetic analysis shows that this particular strain of mice are "wild-type" (ob+) for the leptin gene, and do produce the compound. Based on the parabiosis experiments in mice that we reviewed, explain what might be causing these mice to be obese. What would you examine, to test your hypothesis?

Answer 1

Activity of leptin is dependent on its binding with its receptor, known as leptin receptor (LEPR). LEPR belong to gp130 family of cytokine receptor. After the alternative splicing of LEPR, six different isoforms were formed. These isoforms are LEPRa, LEPRb, LEPRc, LEPRd, LEPRe and LEPRf. Out of these six, LEPRb is the important and longest isoform that has the capacity of strong signaling as compared to others. Thus mutation in the gene encoding for the Leptin Receptor (LEPR) block signal of the leptin received by the brain or the hypothalamus. So due to signal disruption or mutations in the leptin receptor, mice can become obese.

To proof the hypothesis that mutation LEPR could be reason for obesity in mice the

• Quantitative analysis of mRNA of hypothalamus cell of mice brain could be examine
• Sequence of LEPR gene can also be examined to check the mutation as well as for structural configuration of LEPR