Confirmation and Characterization of Murine Body Weight QTLs, <i>Bwq1</i> and <i>Bwq2</i>, Identified in C57BL/6J &times; KK-<i>A</i>^y/<i>a</i> F₂-<i>A</i>^y/<i>a</i> Mice

Abstract

ABSTRACT. Body weight quantitative trait loci (QTLs), Bwq1 and Bwq2, identified previously in C57BL/6J × KK-A y /a F 2 -A y /a mice, were further confirmed and characterized. Body weight measurement was done from 21 days after birth (Day 21) through Day 100, at 10-day intervals. Bwq1 was statistically significant only on Days 40, 50, and 60, whereas Bwq2 was statistically significant on and after Day 40. When body weight gain (WG) between two successive weight measurements was evaluated, both Bwq1 and Bwq2 were statistically significant only for WG between Days 30 and 40. The results suggest that variations in body weight among F 2 -A y /a individuals in later life have been determined by variations in WG during the period shortly after weaning. The results also suggest that Bwq1 is related to increased body weight in the KK strain, because the effect of Bwq1 on the body weight is observed not only in F 2 -A y /a, but also in F 2 -a/a. On the other hand, it is suggested that Bwq2 is related to enhanced obesity caused by A y mutation and therefore is a genetic modifier that specifically interacts with the A y allele, because the effect of Bwq2 is only observed in F 2 -A y /a. There are two candidate genes, Pparg and Hrh1, which are located near the 95% confidence interval of Bwq2, and which are expressed in the adipose tissue; however, we could not find any nucleotide differences in both cDNAs between KK and C57BL/6J strains. KEY WORDS: A y allele, body weight, KK mouse, obesity, quantitative trait locus (QTL).

Quantitative Trait Loci that Control Body Weight and Obesity in an F2 Intercross between C57BL/6J and DDD.Cg-Ay Mice

“…Hrh1 is a plausible candidate gene for body weight QTL identified in the middle of chromosome 6 because Hrh1 constitutes part of the leptin signaling pathway in a way similar to MC4R, and because central administration of histamine decreases body weight and adiposity in A y mice [12]. I could not find any mutations in the coding sequence of Hrh1 in DDD and KK mice [23]. Kim et al [8] also analyzed Hrh1 as a candidate gene, and found no nucleotide changes between TallyHo and B6 alleles.…”

“…For example, Bwq2 [24] and Tabw2 [8] apparently overlap with Bwdq2 and Obdq1 on chromosome 6. We previously identified Bwq2 as a modifier QTL for the A y allele in an F 2 intercross between B6 and obese KK-A y strains [23,24]. Similar to Bwq2, the effects of Bwdq2 and Obdq1 were stronger in F 2 A y than in F 2 non-A y mice.…”

“…The magnitude of phenotypic effects of the A y allele appears to depend on the genetic background, i.e., the location of the A ) mice, and we previously identified a quantitative trait locus (QTL), body weight QTL 2 (Bwq2) [23,24]. Bwq2 is located on the middle of chromosome 6; many gene loci that are relevant to body weight and obesity have been mapped to this chromosome as plausible candidate genes.…”

Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity

“…These include macronutrient intake for carbohydrate (Minc2), which is responsible for preferring carbohydrate to fat in a cross of B6 and CAST/EiJ mice (48), body weight QTL (Bwq2), which is linked to body weight in a cross of B6 and KK-A y (56), and Obq14, which is linked to fat pad weight in a cross of NZO and SM mice (60). Bwq2 has been suggested as a genetic modifier of A y (57). Whether allelic variants at the tabw2 locus are responsible for the phenotypes linked to these QTLs could be determined through a haplotype analysis comparing the TH genotypes with those of the other susceptible and resistant strains (36) or by identification of the molecular bases of these loci.…”

QTL Mapping of Genes Controlling Plasma Insulin and Leptin Concentrations: Metabolic Effect of Obesity QTLs Identified in an F₂ Intercross between C57BL/6J and DDD.Cg-<i>A^y</i> Inbred Mice

“…A congenic mouse strain B6.TH-tabw2/tabw2, which carries obesity QTL tabw2 from the obese TallyHo mouse strain, had increased plasma leptin concentrations compared with control B6.TH-+/+ mice. Interestingly, tabw2 co-localized with Obdq1 [21] and Bwq2 [23,25] on chromosome 6.…”