2026-05-22T16:46:18Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/178922024-09-21T22:58:03Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Alén, Francisco author Gómez-Redondo, Isabel author Rivera, Patricia author Suárez, Juan author Ramos-Ibeas, Priscila author Pericuesta, Eva author Fernández-González, Raul author Perez-Cerezales, Serafín author Horiuchi, Keiko author Orio, Laura author Rodriguez de Fonseca, Fernando author Gutiérrez-Adán, Alfonso 2024-02-10T20:01:56Z 2024-02-10T20:01:56Z 2019-07-19 10.3390/ijms20143543 1422-0067 International journal of molecular sciences http://hdl.handle.net/10668/14277 31331069 http://hdl.handle.net/20.500.12105/17892 Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior. eng U12 introns Zrsr1 Behavior Cell proliferation Hypothalamus Neurogenesis Social interaction Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice. research article