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The ZBED6-IGF2 axis...
The ZBED6-IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals
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- Younis, Shady (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Department of Animal Production, Ain Shams University, Cairo, Egypt
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- Schönke, Milena (författare)
- Department of Molecular Medicine and Surgery, Integrative Physiology, Karolinska Institutet
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- Massart, Julie (författare)
- Department of Molecular Medicine and Surgery, Integrative Physiology, Karolinska Institutet
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- Hjortebjerg, Rikke (författare)
- Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden
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- Sundström, Elisabeth (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Gustafson, Ulla (författare)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Science for Life Laboratory, SciLifeLab
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- Björnholm, Marie (författare)
- Karolinska Institutet
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- Krook, Anna (författare)
- Karolinska Institutet
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Frystyk, Jan (författare)
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- Zierath, Juleen (författare)
- Karolinska Institutet
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- Andersson, Leif (författare)
- Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för medicinsk biokemi och mikrobiologi,Institutionen för husdjursgenetik (HGEN),Department of Animal Breeding and Genetics,Uppsala University,Texas A&M University
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(creator_code:org_t)
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- 2018-02-12
- 2018
- Engelska.
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:9, s. E2048-E2057
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://res.slu.se/i...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- A single nucleotide substitution in the third intron of insulin-like growth factor 2 (IGF2) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation of IGF2 expression in pig skeletal muscle. Here, we investigated the biological significance of ZBED6-IGF2 interaction in the growth of placental mammals using two mouse models, ZBED6 knock-out (Zbed6(-/-)) and Igf2 knock-in mice that carry the pig IGF2 mutation. These transgenic mice exhibit markedly higher serum IGF2 concentrations, higher growth rate, increased lean mass, and larger heart, kidney, and liver; no significant changes were observed for white adipose tissues. The changes in body and lean mass were most pronounced in female mice. The phenotypic changes were concomitant with a remarkable up-regulation of Igf2 expression in adult tissues. Transcriptome analysis of skeletal muscle identified differential expression of genes belonging to the extracellular region category. Expression analysis using fetal muscles indicated a minor role of ZBED6 in regulating Igf2 expression prenatally. Furthermore, transcriptome analysis of the adult skeletal muscle revealed that this elevated expression of Igf2 was derived from the P1 and P2 promoters. The results revealed very similar phenotypic effects in the Zbed6 knock-out mouse and in the Igf2 knock-in mouse, showing that the effect of ZBED6 on growth of muscle and internal organs is mediated through the binding site in the Igf2 gene. The results explain why this ZBED6 binding site is extremely well conserved among placental mammals.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Utvecklingsbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Developmental Biology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Younis, Shady
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Schönke, Milena
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Massart, Julie
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Hjortebjerg, Rik ...
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Sundström, Elisa ...
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Gustafson, Ulla
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visa fler...
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Björnholm, Marie
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Krook, Anna
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Frystyk, Jan
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Zierath, Juleen
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Andersson, Leif
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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och Utvecklingsbiolo ...
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Proceedings of t ...
- Av lärosätet
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Uppsala universitet
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Sveriges Lantbruksuniversitet
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Karolinska Institutet