A 13 amino acid sequence after the transmembrane domain and adjacent to the splicing junction (after lysine 889) of mouse OBRb (long form) was selected for antibody productions .||Obesity, a common nutritional disorder, is associated with diabetes, hypertension, hyperlipidemia, cancer and many other health related problems. At least five genes, Obese (ob), diabetes (db), fat (fat), agouti yellow (Ay), and tubby (tub) have been linked to obesity. Obese gene encodes an adipocyte-tissue derived secreted protein Ob protein/Leptin (146 amino acid, ~16kD) that controls body weight homeostasis. Leptin mediates its effects via the Leptin receptor or Obese receptors (OBR or LEPR) that is expressed in several tissues including hypothalamus. The Ob-R has at least 6 alternatively spliced forms (OBRa-f or LRa-f) that contain a common extracellular domain. The OBRa represents the initially identified mouse Ob-R (short form, 894aa). OBRa, -c, -d, and -f differ in sequence after Lys889 and have short (30-40 aa) cytoplasmic extension Mouse Ob-Rb (long form) displays ~78% homology to the human Ob-R (long form, 1165aa). OBRb has ~300 aa intracellular tail. Expression of Ob-Rb and other forms have been detected in hypothalamus and other tissues. OBRe lacks the transmembrane domain. The soluble Ob-Re is found in adipose tissues, hypothalamus, heart, and testes. Ob-R is abnormally spliced in db/db mice (truncation of cytoplasmic domain) that are important for leptin signaling. Leptin is structurally related to cytokine family and it activates cytokine-like signal transduction by stimulating the JAK-STAT pathway via the OBRb. The absence of functional leptin in ob/ob and the long form OBRb in db/db mice due to abnormal splicing produces severe obesity. The nature of leptin resistance in other obesity models is not clear.

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