title: A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats.
abstract: 1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a < 4.9 cM region between D1Rat461 and D1Rat459. 3. To confirm the assignment of the Dmo1 critical interval, we intercrossed BC5 animals to produce a larger study population (BC5:F1 males; n = 406). For the present study, we used bodyweight at 18 weeks of age as an index of obesity; this phenotype is representative of the closely associated dyslipidaemia and hyperglycaemia phenotypes. 4. Interval mapping assigned logarithm of odds (LOD) peaks at the D1Rat90 marker (LOD = 9.11). One LOD support interval lies within the < 1.7 cM region between D1Rat461 and D1Rat459. 5. This large intercross study confirms that Dmo1 is likely localized within the interval.
authors.affiliation: Otsuka GEN Research Institute, Otsuka Pharmaceutical Co. Ltd., 463-10 Kagasuno, Kawauchi-cho, Tokushima 771-0192, Japan. tkw_watanabe@research.otsuka.co.jp
authors.forename: Takeshi K
authors.initials: TK
authors.lastname: Watanabe
authors.forename: Shiro
authors.initials: S
authors.lastname: Okuno
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Toshihide
authors.initials: T
authors.lastname: Ono
authors.forename: Keiko
authors.initials: K
authors.lastname: Oga
authors.forename: Ayako
authors.initials: A
authors.lastname: Mizoguchi-Miyakita
authors.forename: Hideo
authors.initials: H
authors.lastname: Miyao
authors.forename: Mikio
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Momota
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Goto
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Shinomiya
authors.forename: Haretsugu
authors.initials: H
authors.lastname: Hishigaki
authors.forename: Isamu
authors.initials: I
authors.lastname: Hayashi
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Asai
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Wakitani
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Akira
authors.initials: A
authors.lastname: Tanigami
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001835:Body Weight / Q000235:genetics; D003433:Crosses, Genetic; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006943:Hyperglycemia / Q000235:genetics; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D008297:Male; D009765:Obesity; D010641:Phenotype; D051381:Rats; D011914:Rats, Inbred BN; D020334:Rats, Inbred OLETF