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Maternal influence of prolyl endopeptidase on fat mass of adult progeny.

Warden CH, Fisler JS, Espinal G, Graham J, Havel PJ, Perroud B - Int J Obes (Lond) (2009)

Bottom Line: There were no genotype effects on BW or AI in males or females on either diet.Experiment 2-In contrast, reciprocal crosses of heterozygous males or females with WT B6 revealed highly significant parent of origin effects on all traits except body length.Heterozygosity for PREP GT results in highly significant maternal effects, whereas homozygosity for the PREP(gt/gt) mutation has a much more limited direct effect.

View Article: PubMed Central - PubMed

Affiliation: Rowe Program in Genetics, University of California, Davis, CA 95616, USA. chwarden@ucdavis.edu

ABSTRACT

Background: Maternal genotype has lifetime effects on progeny, but few specific genes, and no proteases, are known to underlie maternal effects. Prolyl endopeptidase (PREP) is a serine protease with putative substrates that regulate appetite or milk production.

Objective: To test effects of PREP on obesity phenotypes in mice.

Design: Mice with a gene trap (GT) of PREP (PREP(gt/gt)) on the C57BL/6J (B6) background were generated. Minimal PREP protein was detected by western blot. In Experiment 1, direct effects of PREP were measured in littermate mice derived from intercrosses of heterozygotes (PREP(WT/gt)). In Experiment 2, maternal effects of PREP were measured in reciprocal crosses of heterozygous (PREP(WT/gt)) and wild-type (WT) (PREP(WT/WT)) males and females. DIETS: Mice were fed either low-fat (LF, Experiments 1 and 2) or high-fat (HF, Experiment 1) defined diets.

Measurements: Adiposity index (AI) was calculated from body weight (BW) and weights of four fat depots measured in 120-day-old mice. Fasting plasma glucose, insulin and leptin were measured. In vivo plasma alpha-MSH levels were measured by targeted quantitative peptidomics.

Results: Experiment 1-In intercross mice, there were significant diet effects, but few genotype effects. There were no genotype effects on BW or AI in males or females on either diet. Experiment 2-In contrast, reciprocal crosses of heterozygous males or females with WT B6 revealed highly significant parent of origin effects on all traits except body length. Progeny (WT and heterozygous genotypes and both sexes) born to female PREP(WT/gt) heterozygotes had fat pads that weighed as much as -twofold more at 120 days old than progeny born to male heterozygotes.

Conclusion: Heterozygosity for PREP GT results in highly significant maternal effects, whereas homozygosity for the PREP(gt/gt) mutation has a much more limited direct effect.

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Related in: MedlinePlus

Maternal obesity effects of the PREP gene-trap mutation on AI in male and female pups. Values are mean ± SE. See Figure 2 legend for methods. There are no significant differences between mice born to PREPWT/gt mothers. The F2 Intercross has only PREPWT/gt heterozygous mothers. Pup genotypes were PREPWT/gt or PREPWT/WT and are combined in this analysis since there was no genotype difference. Male and female heterozygous breeders in the reciprocal cross were littermates of PREPWT/WT × PREPWT/gt crosses.
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Figure 6: Maternal obesity effects of the PREP gene-trap mutation on AI in male and female pups. Values are mean ± SE. See Figure 2 legend for methods. There are no significant differences between mice born to PREPWT/gt mothers. The F2 Intercross has only PREPWT/gt heterozygous mothers. Pup genotypes were PREPWT/gt or PREPWT/WT and are combined in this analysis since there was no genotype difference. Male and female heterozygous breeders in the reciprocal cross were littermates of PREPWT/WT × PREPWT/gt crosses.

Mentions: Progeny from the intercross (Experiment 1) were compared with progeny from the reciprocal cross (Experiment 2) (Figure 6). Pups of both PREPWT/WT and PREPWT/gt genotypes are combined in this analysis since there was no significant effect of pup genotype on adiposity. The results support two conclusions: (1) obesity due to the PREP gene-trap mutation is either additive or dominant since effects are observed when breeding heterozygotes; and (2) data are consistent with maternal effects on obesity. Males cannot be the cause of the obesity phenotype since they cannot both cause leanness in the reciprocal PREPWT/gt male × PREPWT/WT female cross and obesity in the PREPWT/gt male × PREPWT/gt female intercross.


Maternal influence of prolyl endopeptidase on fat mass of adult progeny.

Warden CH, Fisler JS, Espinal G, Graham J, Havel PJ, Perroud B - Int J Obes (Lond) (2009)

Maternal obesity effects of the PREP gene-trap mutation on AI in male and female pups. Values are mean ± SE. See Figure 2 legend for methods. There are no significant differences between mice born to PREPWT/gt mothers. The F2 Intercross has only PREPWT/gt heterozygous mothers. Pup genotypes were PREPWT/gt or PREPWT/WT and are combined in this analysis since there was no genotype difference. Male and female heterozygous breeders in the reciprocal cross were littermates of PREPWT/WT × PREPWT/gt crosses.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2743752&req=5

Figure 6: Maternal obesity effects of the PREP gene-trap mutation on AI in male and female pups. Values are mean ± SE. See Figure 2 legend for methods. There are no significant differences between mice born to PREPWT/gt mothers. The F2 Intercross has only PREPWT/gt heterozygous mothers. Pup genotypes were PREPWT/gt or PREPWT/WT and are combined in this analysis since there was no genotype difference. Male and female heterozygous breeders in the reciprocal cross were littermates of PREPWT/WT × PREPWT/gt crosses.
Mentions: Progeny from the intercross (Experiment 1) were compared with progeny from the reciprocal cross (Experiment 2) (Figure 6). Pups of both PREPWT/WT and PREPWT/gt genotypes are combined in this analysis since there was no significant effect of pup genotype on adiposity. The results support two conclusions: (1) obesity due to the PREP gene-trap mutation is either additive or dominant since effects are observed when breeding heterozygotes; and (2) data are consistent with maternal effects on obesity. Males cannot be the cause of the obesity phenotype since they cannot both cause leanness in the reciprocal PREPWT/gt male × PREPWT/WT female cross and obesity in the PREPWT/gt male × PREPWT/gt female intercross.

Bottom Line: There were no genotype effects on BW or AI in males or females on either diet.Experiment 2-In contrast, reciprocal crosses of heterozygous males or females with WT B6 revealed highly significant parent of origin effects on all traits except body length.Heterozygosity for PREP GT results in highly significant maternal effects, whereas homozygosity for the PREP(gt/gt) mutation has a much more limited direct effect.

View Article: PubMed Central - PubMed

Affiliation: Rowe Program in Genetics, University of California, Davis, CA 95616, USA. chwarden@ucdavis.edu

ABSTRACT

Background: Maternal genotype has lifetime effects on progeny, but few specific genes, and no proteases, are known to underlie maternal effects. Prolyl endopeptidase (PREP) is a serine protease with putative substrates that regulate appetite or milk production.

Objective: To test effects of PREP on obesity phenotypes in mice.

Design: Mice with a gene trap (GT) of PREP (PREP(gt/gt)) on the C57BL/6J (B6) background were generated. Minimal PREP protein was detected by western blot. In Experiment 1, direct effects of PREP were measured in littermate mice derived from intercrosses of heterozygotes (PREP(WT/gt)). In Experiment 2, maternal effects of PREP were measured in reciprocal crosses of heterozygous (PREP(WT/gt)) and wild-type (WT) (PREP(WT/WT)) males and females. DIETS: Mice were fed either low-fat (LF, Experiments 1 and 2) or high-fat (HF, Experiment 1) defined diets.

Measurements: Adiposity index (AI) was calculated from body weight (BW) and weights of four fat depots measured in 120-day-old mice. Fasting plasma glucose, insulin and leptin were measured. In vivo plasma alpha-MSH levels were measured by targeted quantitative peptidomics.

Results: Experiment 1-In intercross mice, there were significant diet effects, but few genotype effects. There were no genotype effects on BW or AI in males or females on either diet. Experiment 2-In contrast, reciprocal crosses of heterozygous males or females with WT B6 revealed highly significant parent of origin effects on all traits except body length. Progeny (WT and heterozygous genotypes and both sexes) born to female PREP(WT/gt) heterozygotes had fat pads that weighed as much as -twofold more at 120 days old than progeny born to male heterozygotes.

Conclusion: Heterozygosity for PREP GT results in highly significant maternal effects, whereas homozygosity for the PREP(gt/gt) mutation has a much more limited direct effect.

Show MeSH
Related in: MedlinePlus