000087839 001__ 87839
000087839 005__ 20230706131404.0
000087839 0247_ $$2doi$$a10.1371/journal.pone.0227411
000087839 0248_ $$2sideral$$a116233
000087839 037__ $$aART-2020-116233
000087839 041__ $$aeng
000087839 100__ $$aBagheri-Fam, S
000087839 245__ $$aThe gene encoding the ketogenic enzyme HMGCS2 displays a unique expression during gonad development in mice
000087839 260__ $$c2020
000087839 5060_ $$aAccess copy available to the general public$$fUnrestricted
000087839 5203_ $$aDisorders/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.
000087839 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B32-17R
000087839 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000087839 590__ $$a3.24$$b2020
000087839 591__ $$aMULTIDISCIPLINARY SCIENCES$$b26 / 72 = 0.361$$c2020$$dQ2$$eT2
000087839 592__ $$a0.99$$b2020
000087839 593__ $$aMultidisciplinary$$c2020$$dQ1
000087839 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000087839 700__ $$aChen, H
000087839 700__ $$aWilson, S
000087839 700__ $$aAyers, K
000087839 700__ $$aHughes, J
000087839 700__ $$aSloan-Bena, F
000087839 700__ $$aCalvel, P
000087839 700__ $$aRobevska, G
000087839 700__ $$0(orcid)0000-0003-0170-7326$$aPuisac, B$$uUniversidad de Zaragoza
000087839 700__ $$aKusz-Zamelczyk, K
000087839 700__ $$aGimelli, S
000087839 700__ $$aSpik, A
000087839 700__ $$aJaruzelska, J
000087839 700__ $$aWarenik-Szymankiewicz, A
000087839 700__ $$aFarad, S
000087839 700__ $$aNef, S
000087839 700__ $$0(orcid)0000-0003-3203-6254$$aPié, J$$uUniversidad de Zaragoza
000087839 700__ $$aThomas, P
000087839 700__ $$aSinclair, A
000087839 700__ $$aWilhelm, D.
000087839 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000087839 773__ $$g15, 1 (2020), e0227411 [23 pp.]$$pPLoS One$$tPLoS ONE$$x1932-6203
000087839 8564_ $$s5144151$$uhttps://zaguan.unizar.es/record/87839/files/texto_completo.pdf$$yVersión publicada
000087839 8564_ $$s493856$$uhttps://zaguan.unizar.es/record/87839/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000087839 909CO $$ooai:zaguan.unizar.es:87839$$particulos$$pdriver
000087839 951__ $$a2023-07-06-12:20:36
000087839 980__ $$aARTICLE