ABSTRACT
Figure 1 Stucture of leptin and defective leptin proteins. The gene for leptin in both humans and rodents encodes a 167amino acid protein with an amino terminal secretory signal sequence of21 amino acids (4). The signal sequence is cleaved during protein processing and leptin circulates in the blood as a 16 kDa protein. In C57BL/61 ob/ob mice a T to C substitution in the first position of codon 105 changes an arginine to a premature stop codon. Two families with mutations in the LEP gene have been identified. In family No.1, a guanine nucleotide in codon 133 is deleted, which results in a frameshift and the synthesis of a truncated leptin protein (91). In the second family a C to T substitution in the first base of codon 105 changes arginine to tryptophan (92). The mutant leptin protein in the ob/ob mouse and in both families is not secreted but is degraded in the adipocyte.
