Metabolic Consequence of Congenital Asplenia Caused by the Dominant hemimelia Mutation in Mice

Abstract

ABSTRACT. The potential roles of the spleen in lipid metabolism have been debated for the last 2 decades. Although there are some discrepancies among investigations, they are in agreement on the point that the spleen has roles in lipid metabolism. In the present study, role of the spleen in lipid metabolism was investigated by use of a hereditary asplenic mouse strain carrying a Dominant hemimelia (Dh) mutation. In studies on females, asplenic mice (Dh/+) had significantly lower plasma high-density lipoprotein-cholesterol (HDL-CHO) levels than did eusplenic mice (+/+) on a chow diet. On a high-fat diet, Dh/+ had significantly higher HDL-CHO than did +/+. In studies on Y-consomic strains (DH-Chr Y), DH-Chr Y-Dh/+ had significantly lower values than did DH-Chr Y-+/+ for all traits. For body weight and HDL-CHO, there were significant differences in mean trait values among DH-Chr Y-+/+, suggesting that Y-linked genes affect these traits. Furthermore, pattern of distribution of mean trait values among Y-consomic strains largely differed between DH-Chr Y-+/+ and DH-Chr Y-Dh/+, suggesting the presence of interaction between Dh and Y-linked genes. The present study shows that Dh has effects on lipid metabolism. Although Dh has multiple phenotypic effects it is possible that the change in lipid levels is affected in part by the absence of the spleen. KEY WORDS: asplenic mouse, Dominant hemimelia (Dh), plasma lipid levels, Y-consomic strains.

Identification of Quantitative Trait Loci That Determine Plasma Total-Cholesterol and Triglyceride Concentrations in DDD/Sgn and C57BL/6J Inbred Mice

“…Based on the studies of Y-consomic mice, the lineage effect was not due to influence by Chr Y [23, 24]. Furthermore, because we observed the lineage effect in the comparison between F 1 females, we concluded that the effect of Chr Y on plasma lipid concentrations is extremely small or nonexistent.…”

Chromosome substitution strains: gene discovery, functional analysis, and systems studies

“…Because Y chromosome and mitochondrial substitutions are made so readily, they have been used for many years to study a variety of traits in many strain combinations (for recent examples, see Barrick et al 2009; Llamas et al 2009; Suto 2009; Nelson et al 2010; Hines et al 2011; Case et al 2012; Kotarska and Styrna 2012). In other instances, an autosomal CSS was made specifically to verify and in some cases localize QTLs with crosses and congenic strains (see, for example, Matin et al 1999; Ochiai et al 2003; Hollis-Moffatt et al 2005; Kumazawa et al 2007; Wang et al 2010; Anderson et al 2009; Trammell et al 2012).…”

“…Other examples of studies based on congenic–consomic strains include modifiers of the spectrum and latency of spontaneous tumors in p53-deficient CSS-19 mice (Ochiai et al 2003), the impact of apslenia on lipid metabolism in CSS-Y strains with the dominant hemimelia Dh mutation (Suto 2009), and modifiers of tumor resistance in NF1-, p53-deficient mice (Barrick et al 2009). …”