Spontaneous mutation in leptin receptor gene leads to development of obesity. (A) Picture of a three months old obese LepRbG506S/G506S and a lean LepRbG506S/+ mouse. (B) Body weight of male and female LepRbG506S/G506S and heterozygous LepRbG506S/+ littermates with age after weaning (n = 3–6/group). (C) Nucleotide and amino acid sequences from Q498 to I511 of wild-type (top) and mutant (bottom) leptin receptor. (D) ARC nuclei from wild-type and homozygous mutants (n = 3/group) were isolated and cDNA prepared. Semiquantitative PCR was performed using oligonucleotides flanking the G506S point mutation and allow identification of both the wild-type (481 bp) and alternatively spliced LepRb (361 bp) products. (E) Body weight of male LepRbG506S/G506S, db/db, and respective heterozygous controls (n = 6–11/group). Values in (B) and (E) show mean ± standard deviation. ***, P < 0.0021, ****, P < 0.0002.