Identification of Additional Body Weight QTLs in the Berlin Fat Mouse BFMI861 Lines Using Time Series Data

Overview

Journal Sci Rep

Specialty Science

Date 2024 Mar 15

PMID 38486030

Authors

Manuel Delpero

Paula Korkuc

Danny Arends

Gudrun A Brockmann

Deike Hesse

Affiliations

Soon will be listed here.

Abstract

The Berlin Fat Mouse Inbred line (BFMI) is a model for obesity and metabolic syndrome. The sublines BFMI861-S1 and BFMI861-S2 differ in weight despite high genetic similarity and a shared obesity-related locus. This study focused on identifying additional body weight quantitative trait loci (QTLs) by analyzing weekly weight measurements in a male population of the advanced intercross line BFMI861-S1 x BFMI861-S2. QTL analysis, utilizing 200 selectively genotyped mice (GigaMUGA) and 197 males genotyped for top SNPs, revealed a genome-wide significant QTL on Chr 15 (68.46 to 81.40 Mb) for body weight between weeks 9 to 20. Notably, this QTL disappeared (weeks 21 to 23) and reappeared (weeks 24 and 25) coinciding with a diet change. Additionally, a significant body weight QTL on Chr 16 (3.89 to 22.79 Mb) was identified from weeks 6 to 25. Candidate genes, including Gpt, Cbx6, Apol6, Apol8, Sun2 (Chr 15) and Trap1, Rrn3, Mapk1 (Chr 16), were prioritized. This study unveiled two additional body weight QTLs, one of which is novel and responsive to diet changes. These findings illuminate genomic regions influencing weight in BFMI and emphasize the utility of time series data in uncovering novel genetic factors.

References

Krause F, Mohebian K, Delpero M, Hesse D, Kuhn R, Arends D . A deletion containing a CTCF-element in intron 8 of the Bbs7 gene is partially responsible for juvenile obesity in the Berlin Fat Mouse. Mamm Genome. 2021; 33(3):465-470. PMC: 9360062. DOI: 10.1007/s00335-021-09938-5. View

Moorefield B, GREENE E, Reeder R . RNA polymerase I transcription factor Rrn3 is functionally conserved between yeast and human. Proc Natl Acad Sci U S A. 2000; 97(9):4724-9. PMC: 18300. DOI: 10.1073/pnas.080063997. View

Simmonds M, Llewellyn A, Owen C, Woolacott N . Predicting adult obesity from childhood obesity: a systematic review and meta-analysis. Obes Rev. 2015; 17(2):95-107. DOI: 10.1111/obr.12334. View

Delpero M, Arends D, Freiberg A, Brockmann G, Hesse D . QTL-mapping in the obese Berlin Fat Mouse identifies additional candidate genes for obesity and fatty liver disease. Sci Rep. 2022; 12(1):10471. PMC: 9213485. DOI: 10.1038/s41598-022-14316-5. View

Lund M, Sorensen P, Madsen P, Jaffrezic F . Detection and modelling of time-dependent QTL in animal populations. Genet Sel Evol. 2008; 40(2):177-94. PMC: 2674924. DOI: 10.1186/1297-9686-40-2-177. View

Lisanti S, Tavecchio M, Chae Y, Liu Q, Brice A, Thakur M . Deletion of the mitochondrial chaperone TRAP-1 uncovers global reprogramming of metabolic networks. Cell Rep. 2014; 8(3):671-7. PMC: 4127146. DOI: 10.1016/j.celrep.2014.06.061. View

Schmitt A, Bortfeldt R, Neuschl C, Brockmann G . RandoMate: a program for the generation of random mating schemes for small laboratory animals. Mamm Genome. 2009; 20(5):321-5. DOI: 10.1007/s00335-009-9185-6. View

Duchateau P, Movsesyan I, Yamashita S, Sakai N, Hirano K, Schoenhaus S . Plasma apolipoprotein L concentrations correlate with plasma triglycerides and cholesterol levels in normolipidemic, hyperlipidemic, and diabetic subjects. J Lipid Res. 2000; 41(8):1231-6. View

Maik-Rachline G, Wortzel I, Seger R . Alternative Splicing of MAPKs in the Regulation of Signaling Specificity. Cells. 2021; 10(12). PMC: 8699841. DOI: 10.3390/cells10123466. View

10.

Cavanaugh A, Hirschler-Laszkiewicz I, Hu Q, Dundr M, Smink T, Misteli T . Rrn3 phosphorylation is a regulatory checkpoint for ribosome biogenesis. J Biol Chem. 2002; 277(30):27423-32. DOI: 10.1074/jbc.M201232200. View

11.

Fang C, Chen M, Chang T, Wu C, Chang J, Huang H . and Are Affected by Stretch in HL-1 Atrial Myocytes. Int J Mol Sci. 2018; 19(12). PMC: 6321625. DOI: 10.3390/ijms19124094. View

12.

Locke A, Kahali B, Berndt S, Justice A, Pers T, Day F . Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015; 518(7538):197-206. PMC: 4382211. DOI: 10.1038/nature14177. View

13.

Wengert L, Backe S, Bourboulia D, Mollapour M, Woodford M . TRAP1 Chaperones the Metabolic Switch in Cancer. Biomolecules. 2022; 12(6). PMC: 9221471. DOI: 10.3390/biom12060786. View

14.

Gao X . Multiple testing corrections for imputed SNPs. Genet Epidemiol. 2011; 35(3):154-8. PMC: 3055936. DOI: 10.1002/gepi.20563. View

15.

Xue W, Zhang H, Fan Y, Xiao Z, Zhao Y, Liu W . Upregulation of Apol8 by Epothilone D facilitates the neuronal relay of transplanted NSCs in spinal cord injury. Stem Cell Res Ther. 2021; 12(1):300. PMC: 8157417. DOI: 10.1186/s13287-021-02375-w. View

16.

McLaren W, Gil L, Hunt S, Riat H, Ritchie G, Thormann A . The Ensembl Variant Effect Predictor. Genome Biol. 2016; 17(1):122. PMC: 4893825. DOI: 10.1186/s13059-016-0974-4. View

17.

Mohebian K, Hesse D, Arends D, Brockmann G . A 5' UTR Mutation Contributes to Down-Regulation of in the Berlin Fat Mouse. Int J Mol Sci. 2022; 23(21). PMC: 9658298. DOI: 10.3390/ijms232113018. View

18.

Dupuis J, Siegmund D . Statistical methods for mapping quantitative trait loci from a dense set of markers. Genetics. 1999; 151(1):373-86. PMC: 1460471. DOI: 10.1093/genetics/151.1.373. View

19.

Pena-Romero A, Navas-Carrillo D, Marin F, Orenes-Pinero E . The future of nutrition: Nutrigenomics and nutrigenetics in obesity and cardiovascular diseases. Crit Rev Food Sci Nutr. 2017; 58(17):3030-3041. DOI: 10.1080/10408398.2017.1349731. View

20.

Delpero M, Arends D, Sprechert M, Krause F, Kluth O, Schurmann A . Identification of four novel QTL linked to the metabolic syndrome in the Berlin Fat Mouse. Int J Obes (Lond). 2021; 46(2):307-315. PMC: 8794782. DOI: 10.1038/s41366-021-00991-3. View