Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice
In farmed animals, carcass weight represents an important economic trait. Since we had demonstrated that IGFBP-2 represents a potent inhibitor of muscle accretion in inbred mice, we wanted to quantify the inhibitory effects of IGFBP-2 under conditions of elevated protein mass in growth selected non-...
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MDPI AG
2020-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/10/2174 |
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| author | Daniela Ohde Michael Walz Christina Walz Antonia Noce Julia Brenmoehl Martina Langhammer Andreas Hoeflich |
| author_facet | Daniela Ohde Michael Walz Christina Walz Antonia Noce Julia Brenmoehl Martina Langhammer Andreas Hoeflich |
| author_sort | Daniela Ohde |
| collection | DOAJ |
| description | In farmed animals, carcass weight represents an important economic trait. Since we had demonstrated that IGFBP-2 represents a potent inhibitor of muscle accretion in inbred mice, we wanted to quantify the inhibitory effects of IGFBP-2 under conditions of elevated protein mass in growth selected non-inbred mice (DU6P). Therefore, we crossed male DU6P mice with female IGFBP-2 transgenic mice. Male IGFBP-2 transgenic offspring (DU6P/IGFBP-2) were characterized by more than 20% reductions of carcass mass compared to male non-transgenic littermates. The carcass mass in males was also significantly lower (<i>p</i> < 0.001) than in transgenic female DU6P/IGFBP-2 mice, which showed a reduction of less than 10% (<i>p</i> < 0.05) compared to non-transgenic female DU6P/IGFBP-2 mice. Although transgene expression was elevated in the muscle of both sexes (<i>p</i> < 0.001), serum levels were normal in female, but significantly reduced in male transgenic DU6P/IGFBP-2 mice (<i>p</i> < 0.001). In this group, also IGFBP-3 and IGFBP-4 were significantly reduced in the circulation (<i>p</i> < 0.01). Particularly in male transgenic mice, we were able to identify proteolytic activity against recombinant IGFBP-2 included in diluted serum. IGFBP-proteolysis in males correlated with massive reductions of IGF-1 in serum samples and the presence of elevated levels of IGFBP-2 fragments. From our data, we conclude that elevated tissue expression of IGFBP-2 is an essential effector of muscle accretion and may block more than 20% of carcass mass. However, in the circulation, intact IGFBP-2 contained no reliable biomarker content. Notably, for the estimation of breeding values in meat-producing animal species, monitoring of IGFBP-2 expression in muscle appears to be supported by the present study in a model system. |
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| last_indexed | 2024-03-10T16:01:34Z |
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| spelling | doaj.art-380903685a944fa0818099d030cfb0362023-11-20T15:11:48ZengMDPI AGCells2073-44092020-09-01910217410.3390/cells9102174Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic MiceDaniela Ohde0Michael Walz1Christina Walz2Antonia Noce3Julia Brenmoehl4Martina Langhammer5Andreas Hoeflich6Institute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genetics and Biometry, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyInstitute of Genome Biology, Leibniz-Institute for Farm Animal Biology (FBN), 18196 Dummerstorf, GermanyIn farmed animals, carcass weight represents an important economic trait. Since we had demonstrated that IGFBP-2 represents a potent inhibitor of muscle accretion in inbred mice, we wanted to quantify the inhibitory effects of IGFBP-2 under conditions of elevated protein mass in growth selected non-inbred mice (DU6P). Therefore, we crossed male DU6P mice with female IGFBP-2 transgenic mice. Male IGFBP-2 transgenic offspring (DU6P/IGFBP-2) were characterized by more than 20% reductions of carcass mass compared to male non-transgenic littermates. The carcass mass in males was also significantly lower (<i>p</i> < 0.001) than in transgenic female DU6P/IGFBP-2 mice, which showed a reduction of less than 10% (<i>p</i> < 0.05) compared to non-transgenic female DU6P/IGFBP-2 mice. Although transgene expression was elevated in the muscle of both sexes (<i>p</i> < 0.001), serum levels were normal in female, but significantly reduced in male transgenic DU6P/IGFBP-2 mice (<i>p</i> < 0.001). In this group, also IGFBP-3 and IGFBP-4 were significantly reduced in the circulation (<i>p</i> < 0.01). Particularly in male transgenic mice, we were able to identify proteolytic activity against recombinant IGFBP-2 included in diluted serum. IGFBP-proteolysis in males correlated with massive reductions of IGF-1 in serum samples and the presence of elevated levels of IGFBP-2 fragments. From our data, we conclude that elevated tissue expression of IGFBP-2 is an essential effector of muscle accretion and may block more than 20% of carcass mass. However, in the circulation, intact IGFBP-2 contained no reliable biomarker content. Notably, for the estimation of breeding values in meat-producing animal species, monitoring of IGFBP-2 expression in muscle appears to be supported by the present study in a model system.https://www.mdpi.com/2073-4409/9/10/2174IGFBP-2sextransgenic mousephenotype selectionmuscle accretioncarcass weight |
| spellingShingle | Daniela Ohde Michael Walz Christina Walz Antonia Noce Julia Brenmoehl Martina Langhammer Andreas Hoeflich Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice Cells IGFBP-2 sex transgenic mouse phenotype selection muscle accretion carcass weight |
| title | Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice |
| title_full | Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice |
| title_fullStr | Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice |
| title_full_unstemmed | Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice |
| title_short | Sex-Specific Control of Muscle Mass: Elevated IGFBP Proteolysis and Reductions of IGF-1 Levels Are Associated with Substantial Loss of Carcass Weight in Male DU6PxIGFBP-2 Transgenic Mice |
| title_sort | sex specific control of muscle mass elevated igfbp proteolysis and reductions of igf 1 levels are associated with substantial loss of carcass weight in male du6pxigfbp 2 transgenic mice |
| topic | IGFBP-2 sex transgenic mouse phenotype selection muscle accretion carcass weight |
| url | https://www.mdpi.com/2073-4409/9/10/2174 |
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