caa a22 4500 475771648 CHVBK 20180406123619.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s001250051570 doi (NATIONALLICENCE)springer-10.1007/s001250051570 Quantitative trait loci for obesity and insulin resistance (Nob1, Nob2) and their interaction with the leptin receptor allele (LeprA720T/T1044I) in New Zealand obese mice [Elektronische Daten] [R. Kluge, K. Giesen, G. Bahrenberg, L. Plum, J. R. Ortlepp, H.-G. Joost] Abstract : Aims/hypothesis. To locate genes responsible for obesity and insulin resistance, a backcross model of New Zealand obese (NZO) mice with the lean Swiss/Jackson Laboratory (SJL) strain was stablished. Results. In female NZO x F1 backcross mice, two major quantitative trait loci for variables of obesity (body weight, body mass index, total body fat) and insulin resistance (hyperinsulinaemia) were identified on chromosomes 5 (Nob1) and 19 (Nob2) close to the markers D5Mit392 and D19Mit91. The aberrant alleles have presumably contributed by the NZO genome. Whereas Nob1 contributed mainly to higher body weight, Nob2 seemed to mainly aggravate insulin resistance independent of obesity. The leptin receptor variant of NZO (Lepr A720T/T1044I) failed to alter any of the variables of obesity. It seemed, however, to enhance the effect of Nob1 on body weight and that of Nob2 on serum insulin concentration. When expressed in COS-7 cells, Lepr A720T/T1044I produced a normal basal and maximum activation with a minor increase in the EC50 of leptin. Conclusions/interpretation. The data identify two new quantitative trait loci that are responsible for a major part of obesity and hyperinsulinaemia as produced by recessive genes in NZO mice. Lepr A720T/T1044I alone cannot produce obesity, but may enhance the effects of other obesity/insulin resistance genes in this mouse model. [Diabetologia (2000) 43: 1565-1572] Springer-Verlag Berlin Heidelberg, 2000 Keywords Obesity nationallicence insulin resistance nationallicence New Zealand obese mouse nationallicence quantitative trait locus nationallicence leptin receptor nationallicence Kluge R. Institute of Animal Research, Medical Faculty of the Technical University, Aachen, Germany, DE aut Giesen K. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut Bahrenberg G. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut Plum L. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut Ortlepp J. R. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut Joost H.-G Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut https://doi.org/10.1007/s001250051570 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051570 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kluge R. Institute of Animal Research, Medical Faculty of the Technical University, Aachen, Germany, DE aut NATIONALLICENCE 700 1- Giesen K. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut NATIONALLICENCE 700 1- Bahrenberg G. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut NATIONALLICENCE 700 1- Plum L. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut NATIONALLICENCE 700 1- Ortlepp J. R. Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut NATIONALLICENCE 700 1- Joost H.-G Institute of Pharmacology, Medical Faculty of the Technical University, Aachen, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer