title: Alleles on rat chromosome 4 (D4Got41-Fabp1/Tacr1) regulate subphenotypes of obesity.
abstract: OBJECTIVE
  The use of inbred animal models is an essential component of the genetic dissection of complex diseases. Because quantitative trait loci for serum triglycerides, total cholesterol, and body weight were mapped on chromosome 4 in a cross of BioBreeding/OttawaKarlsburg (BB/OK) and spontaneously hypertensive (SHR) rats, we established a congenic BB.SHR rat strain by introgressing a SHR segment of chromosome 4 (D4Got41-Tacr1) into a BB/OK background. The phenotype of these BB.SHR rats (BB.4S) confirmed the quantitative trait loci. To discover whether the phenotype of BB.4S can only be attributed to the SHR segment per se, we established an additional congenic BB.WOKW strain by introgressing a similar segment of chromosome 4 (D4Got41-Fabp1) of the Wistar Ottawa Karlsburg RT1(u) rat into a BB/OK background, termed briefly BB.4W.
  
  
  METHODS
  Male normoglycemic BB/OK (20), BB.4S (20), and BB.4W (16) rats were longitudinally studied for body weight, serum triglycerides, total and high-density lipoprotein-cholesterol, and glucose tolerance. At the end of the observation period (32 weeks), serum insulin, leptin, and adiposity index (AI) were determined.
  
  
  CONCLUSIONS
  Congenic BB.4S and BB.4W were significantly heavier, and AI, serum triglycerides, and total cholesterol values were significantly elevated in BB.4S and BB.4W compared with BB/OK but more pronounced in BB.4S. The highest serum insulin was found in BB.4W and highest leptin in BB.4S. Because the body weight gain and AI were comparable between BB.4S and BB.4W, the obviously higher insulin levels in BB.4W and higher leptin values in BB.4S suggest that the two congenics most probably define two subphenotypes of obesity and provide the unique opportunity to study their genetics.
authors.affiliation: Department of Laboratory Animal Science, Medical Faculty, University of Greifswald, Karlsburg, Germany. kloeting@uni-greifswald.de
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.forename: Barbara
authors.initials: B
authors.lastname: Wilke
authors.forename: Ingrid
authors.initials: I
authors.lastname: Klöting
mesh_terms: D000483:Alleles; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D051381:Rats; D011913:Rats, Inbred BB; D011918:Rats, Inbred SHR; D014280:Triglycerides / Q000097:blood
chemical_list: D008076:Cholesterol, HDL; D007328:Insulin; D020738:Leptin; D014280:Triglycerides