Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice

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Alén Fariñas, Francisco and Gómez-Redondo, Isabel and Rivera, Patricia and Suárez, Juan and Ramos-Ibeas, Priscila and Pericuesta, Eva and Fernández-González, Raul and Perez-Cerezales, Serafín and Horiuchi, Keiko and Orio Ortiz, Laura and Rodriguez de Fonseca, Fernando and Gutiérrez-Adán, Alfonso (2019) Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice. International Journal of Molecular Sciences, 20 (14). p. 3543. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms20143543



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Zrsr1; U12 introns; hypothalamus; behavior; social interaction; neurogenesis; cell proliferation
Subjects:Medical sciences > Psychology
Medical sciences > Psychology > Experimental psychology
ID Code:62071
Deposited On:10 Sep 2020 12:03
Last Modified:17 Apr 2021 09:27

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