The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice.
Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a met...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0227411&type=printable |
| _version_ | 1826574254791983104 |
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| author | Stefan Bagheri-Fam Huijun Chen Sean Wilson Katie Ayers James Hughes Frederique Sloan-Bena Pierre Calvel Gorjana Robevska Beatriz Puisac Kamila Kusz-Zamelczyk Stefania Gimelli Anna Spik Jadwiga Jaruzelska Alina Warenik-Szymankiewicz Sultana Faradz Serge Nef Juan Pié Paul Thomas Andrew Sinclair Dagmar Wilhelm |
| author_facet | Stefan Bagheri-Fam Huijun Chen Sean Wilson Katie Ayers James Hughes Frederique Sloan-Bena Pierre Calvel Gorjana Robevska Beatriz Puisac Kamila Kusz-Zamelczyk Stefania Gimelli Anna Spik Jadwiga Jaruzelska Alina Warenik-Szymankiewicz Sultana Faradz Serge Nef Juan Pié Paul Thomas Andrew Sinclair Dagmar Wilhelm |
| author_sort | Stefan Bagheri-Fam |
| collection | DOAJ |
| description | Disorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a metabolic enzyme in the liver important for energy production from fatty acids, that shows an unusual expression pattern in developing fetal mouse gonads. Shortly after gonadal sex determination it is up-regulated in the developing testes following a very similar spatial and temporal pattern as the male-determining gene Sry in Sertoli cells before switching to ovarian enriched expression. To test if Hmgcs2 is important for gonad development in mammals, we pursued two lines of investigations. Firstly, we generated Hmgcs2-null mice using CRISPR/Cas9 and found that these mice had gonads that developed normally even on a sensitized background. Secondly, we screened 46,XY DSD patients with gonadal dysgenesis and identified two unrelated patients with a deletion and a deleterious missense variant in HMGCS2 respectively. However, both variants were heterozygous, suggesting that HMGCS2 might not be the causative gene. Analysis of a larger number of patients in the future might shed more light into the possible association of HMGCS2 with human gonadal development. |
| first_indexed | 2024-12-16T07:32:42Z |
| format | Article |
| id | doaj.art-1d69a154859b4aa693da7b441971531f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2025-03-14T12:55:53Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1d69a154859b4aa693da7b441971531f2025-03-02T05:33:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01151e022741110.1371/journal.pone.0227411The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice.Stefan Bagheri-FamHuijun ChenSean WilsonKatie AyersJames HughesFrederique Sloan-BenaPierre CalvelGorjana RobevskaBeatriz PuisacKamila Kusz-ZamelczykStefania GimelliAnna SpikJadwiga JaruzelskaAlina Warenik-SzymankiewiczSultana FaradzSerge NefJuan PiéPaul ThomasAndrew SinclairDagmar WilhelmDisorders/differences of sex development (DSD) cause profound psychological and reproductive consequences for the affected individuals, however, most are still unexplained at the molecular level. Here, we present a novel gene, 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), encoding a metabolic enzyme in the liver important for energy production from fatty acids, that shows an unusual expression pattern in developing fetal mouse gonads. Shortly after gonadal sex determination it is up-regulated in the developing testes following a very similar spatial and temporal pattern as the male-determining gene Sry in Sertoli cells before switching to ovarian enriched expression. To test if Hmgcs2 is important for gonad development in mammals, we pursued two lines of investigations. Firstly, we generated Hmgcs2-null mice using CRISPR/Cas9 and found that these mice had gonads that developed normally even on a sensitized background. Secondly, we screened 46,XY DSD patients with gonadal dysgenesis and identified two unrelated patients with a deletion and a deleterious missense variant in HMGCS2 respectively. However, both variants were heterozygous, suggesting that HMGCS2 might not be the causative gene. Analysis of a larger number of patients in the future might shed more light into the possible association of HMGCS2 with human gonadal development.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0227411&type=printable |
| spellingShingle | Stefan Bagheri-Fam Huijun Chen Sean Wilson Katie Ayers James Hughes Frederique Sloan-Bena Pierre Calvel Gorjana Robevska Beatriz Puisac Kamila Kusz-Zamelczyk Stefania Gimelli Anna Spik Jadwiga Jaruzelska Alina Warenik-Szymankiewicz Sultana Faradz Serge Nef Juan Pié Paul Thomas Andrew Sinclair Dagmar Wilhelm The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. PLoS ONE |
| title | The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. |
| title_full | The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. |
| title_fullStr | The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. |
| title_full_unstemmed | The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. |
| title_short | The gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice. |
| title_sort | gene encoding the ketogenic enzyme hmgcs2 displays a unique expression during gonad development in mice |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0227411&type=printable |
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