Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors
IntroductionPorcine congenital splay leg syndrome (PCS) is a major birth defect in piglets, resulting in lameness and high mortality rates. The multifactorial pathogenesis of PSC is not well understood but includes a polygenic inheritance.MethodsHere, in addition to morphological investigations, we...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-11-01
|
| Series: | Frontiers in Veterinary Science |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2023.1028879/full |
| _version_ | 1797448107250679808 |
|---|---|
| author | Toni Schumacher Henry Reyer Steffen Maak Monika Röntgen |
| author_facet | Toni Schumacher Henry Reyer Steffen Maak Monika Röntgen |
| author_sort | Toni Schumacher |
| collection | DOAJ |
| description | IntroductionPorcine congenital splay leg syndrome (PCS) is a major birth defect in piglets, resulting in lameness and high mortality rates. The multifactorial pathogenesis of PSC is not well understood but includes a polygenic inheritance.MethodsHere, in addition to morphological investigations, we characterized the expression of myogenic genes and functional (proliferation and differentiation) properties of myogenic precursor/satellite cells (SATCs) in 1 day-old PCS piglets, non-affected littermates (LCs), and piglets from PCS-free healthy litters (HCs). In addition, PCS phenotypes were related to the SNP Homer1_rs325197091 within the Homer1 locus, which has been identified as a potential hereditary cause of PCS.Results and discussionSamples from musculus semitendinosus (ST) of PCS piglets had a higher proportion of type II fibers, reflecting myofiber immaturity. In addition, myofiber atrophy, a lower number of myonuclei per fiber (ST), and a higher apoptotic activity (in ST and longissimus dorsi muscle; LD) were found in the PCS group. A higher proportion of cycling committed myoblasts (Pax7+/Ki67+ cells) occurred in samples from PCS-affected piglets, and on the other hand, the mRNA expression of genes involved in differentiation (muscle differentiation 1; MyoD, myogenin; MyoG) was repressed compared with HCs. Cultured SATCs from PCS-affected animals showed a temporal shift in peak expression of Pax7, MyoD, and MyoG toward days 3 and 4 of their 7 days differentiation regime. In vitro experiments with isolated SATCs confirmed the lower differentiation potential and the delayed progression of the myogenic processes in cells from piglets with PCS phenotype. In addition, Pax7 and desmin were differently expressed in Homer1_rs325197091 genotype variants (GG, GA, and AA). Both genes showed the lowest expression in the homozygous AA-variant, which was most frequently found in PCS-affected animals. The homozygous AA-variant was also associated with lower expression of the truncated Homer1-subtype 205. Thus, we hypothesize that in PCS, the balance between Homer1 proteins and its signaling functions is changed in a way detrimental to the myogenic differentiation program. Our results demonstrated direct negative effects of the Homer1 AA genotype on Pax7 expression, but the exact mode of action still needs to be elucidated. |
| first_indexed | 2024-03-09T14:05:35Z |
| format | Article |
| id | doaj.art-312ff2de04df4e4eb5dabb38b9555d80 |
| institution | Directory Open Access Journal |
| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-03-09T14:05:35Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-312ff2de04df4e4eb5dabb38b9555d802023-11-30T04:50:13ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692023-11-011010.3389/fvets.2023.10288791028879Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitorsToni Schumacher0Henry Reyer1Steffen Maak2Monika Röntgen3Institute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyInstitute of Genome Biology, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyInstitute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyInstitute of Muscle Biology and Growth, Research Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyIntroductionPorcine congenital splay leg syndrome (PCS) is a major birth defect in piglets, resulting in lameness and high mortality rates. The multifactorial pathogenesis of PSC is not well understood but includes a polygenic inheritance.MethodsHere, in addition to morphological investigations, we characterized the expression of myogenic genes and functional (proliferation and differentiation) properties of myogenic precursor/satellite cells (SATCs) in 1 day-old PCS piglets, non-affected littermates (LCs), and piglets from PCS-free healthy litters (HCs). In addition, PCS phenotypes were related to the SNP Homer1_rs325197091 within the Homer1 locus, which has been identified as a potential hereditary cause of PCS.Results and discussionSamples from musculus semitendinosus (ST) of PCS piglets had a higher proportion of type II fibers, reflecting myofiber immaturity. In addition, myofiber atrophy, a lower number of myonuclei per fiber (ST), and a higher apoptotic activity (in ST and longissimus dorsi muscle; LD) were found in the PCS group. A higher proportion of cycling committed myoblasts (Pax7+/Ki67+ cells) occurred in samples from PCS-affected piglets, and on the other hand, the mRNA expression of genes involved in differentiation (muscle differentiation 1; MyoD, myogenin; MyoG) was repressed compared with HCs. Cultured SATCs from PCS-affected animals showed a temporal shift in peak expression of Pax7, MyoD, and MyoG toward days 3 and 4 of their 7 days differentiation regime. In vitro experiments with isolated SATCs confirmed the lower differentiation potential and the delayed progression of the myogenic processes in cells from piglets with PCS phenotype. In addition, Pax7 and desmin were differently expressed in Homer1_rs325197091 genotype variants (GG, GA, and AA). Both genes showed the lowest expression in the homozygous AA-variant, which was most frequently found in PCS-affected animals. The homozygous AA-variant was also associated with lower expression of the truncated Homer1-subtype 205. Thus, we hypothesize that in PCS, the balance between Homer1 proteins and its signaling functions is changed in a way detrimental to the myogenic differentiation program. Our results demonstrated direct negative effects of the Homer1 AA genotype on Pax7 expression, but the exact mode of action still needs to be elucidated.https://www.frontiersin.org/articles/10.3389/fvets.2023.1028879/fullporcine congenital splay legPCSSNPhomer1myogenesis |
| spellingShingle | Toni Schumacher Henry Reyer Steffen Maak Monika Röntgen Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors Frontiers in Veterinary Science porcine congenital splay leg PCS SNP homer1 myogenesis |
| title | Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors |
| title_full | Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors |
| title_fullStr | Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors |
| title_full_unstemmed | Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors |
| title_short | Homer 1 genotype AA variant relates to congenital splay leg syndrome in piglets by repressing Pax7 in myogenic progenitors |
| title_sort | homer 1 genotype aa variant relates to congenital splay leg syndrome in piglets by repressing pax7 in myogenic progenitors |
| topic | porcine congenital splay leg PCS SNP homer1 myogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2023.1028879/full |
| work_keys_str_mv | AT tonischumacher homer1genotypeaavariantrelatestocongenitalsplaylegsyndromeinpigletsbyrepressingpax7inmyogenicprogenitors AT henryreyer homer1genotypeaavariantrelatestocongenitalsplaylegsyndromeinpigletsbyrepressingpax7inmyogenicprogenitors AT steffenmaak homer1genotypeaavariantrelatestocongenitalsplaylegsyndromeinpigletsbyrepressingpax7inmyogenicprogenitors AT monikarontgen homer1genotypeaavariantrelatestocongenitalsplaylegsyndromeinpigletsbyrepressingpax7inmyogenicprogenitors |