RT Journal Article
T1 Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice
A1 Alén Fariñas, Francisco
A1 Gómez-Redondo, Isabel
A1 Rivera, Patricia
A1 Suárez, Juan
A1 Ramos-Ibeas, Priscila
A1 Pericuesta, Eva
A1 Fernández-González, Raul
A1 Perez-Cerezales, Serafín
A1 Horiuchi, Keiko
A1 Orio Ortiz, Laura
A1 Rodríguez De Fonseca, Fernando Antonio
A1 Gutiérrez-Adán, Alfonso
AB 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.
SN 1422-0067
YR 2019
FD 2019
LK https://hdl.handle.net/20.500.14352/12393
UL https://hdl.handle.net/20.500.14352/12393
LA eng
NO Ministerio de Ciencia e Innovación (MICINN)
DS Docta Complutense
RD 10 may 2025