The insertion of Neomycin cassette impairs maternal and social behaviors in Arc/Arg3.1 knock-out mice

Fuente: arXiv

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Bibliographic Details
Main Authors:	Dudas, Ana, Caire, Emilia, Kuku, Abdurahman Hassan a, Azzopardi, Nicolas, Annamneedi, Anil, Elseedy, Heba, Lefort, Gaëlle, Piegu, Benoît, Yvinec, Romain, Pecnard, Emmanuel, Drobecq, Lucile, Trouillet, Anne-Charlotte, Sirigu, Angela, Kuhl, Dietmar, Chamero, Pablo, Ohana, Ora, Pellissier, Lucie P.
Format:	Preprint
Published:	2025
Subjects:	Neurons and Cognition
Online Access:	Acceder al recurso
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_version_	1866908351665799168
author	Dudas, Ana Caire, Emilia Kuku, Abdurahman Hassan a Azzopardi, Nicolas Annamneedi, Anil Elseedy, Heba Lefort, Gaëlle Piegu, Benoît Yvinec, Romain Pecnard, Emmanuel Drobecq, Lucile Trouillet, Anne-Charlotte Sirigu, Angela Kuhl, Dietmar Chamero, Pablo Ohana, Ora Pellissier, Lucie P.
author_facet	Dudas, Ana Caire, Emilia Kuku, Abdurahman Hassan a Azzopardi, Nicolas Annamneedi, Anil Elseedy, Heba Lefort, Gaëlle Piegu, Benoît Yvinec, Romain Pecnard, Emmanuel Drobecq, Lucile Trouillet, Anne-Charlotte Sirigu, Angela Kuhl, Dietmar Chamero, Pablo Ohana, Ora Pellissier, Lucie P.
contents	The Neomycin resistance cassette (Neo+) is commonly inserted in the genome of mice to generate knock-out (KO) models. The effect of gene deletion on social behaviors in mice is controversial between studies using different Neo+ and Neo-mouse lines, particularly Arc/Arg3.1 KO lines. In this study, we identified severe maternal behavior impairments in Neo+, but not Neo-Arc/Arg3.1 KO dams. These deficits resulted from reduced sociability and abnormal social information processing in Neo+ Arc/Arg3.1 KO dams, exacerbated by social communication impairments in pups. The expression of the Neo cassette product did not cause cytotoxicity, but led to altered ERK signaling, gene expression, and oxytocin system. However, oxytocin administration did not improve social impairments in Neo+ Arc/Arg3.1 KO animals. Interestingly, early social environment enrichment enhanced social interaction with familiar, but not unfamiliar conspecifics or maternal behavior. Overall, our findings reveal a major impact of the Neo cassette on behaviors, particularly social behaviors, in Arc/Arg3.1 KO mice, underscoring the need to re-examine phenotypes of animal models carrying the Neo cassette in neuroscience research.
format	Preprint
id	arxiv_https___arxiv_org_abs_2505_03339
institution	arXiv
publishDate	2025
record_format	arxiv
spellingShingle	The insertion of Neomycin cassette impairs maternal and social behaviors in Arc/Arg3.1 knock-out mice Dudas, Ana Caire, Emilia Kuku, Abdurahman Hassan a Azzopardi, Nicolas Annamneedi, Anil Elseedy, Heba Lefort, Gaëlle Piegu, Benoît Yvinec, Romain Pecnard, Emmanuel Drobecq, Lucile Trouillet, Anne-Charlotte Sirigu, Angela Kuhl, Dietmar Chamero, Pablo Ohana, Ora Pellissier, Lucie P. Neurons and Cognition The Neomycin resistance cassette (Neo+) is commonly inserted in the genome of mice to generate knock-out (KO) models. The effect of gene deletion on social behaviors in mice is controversial between studies using different Neo+ and Neo-mouse lines, particularly Arc/Arg3.1 KO lines. In this study, we identified severe maternal behavior impairments in Neo+, but not Neo-Arc/Arg3.1 KO dams. These deficits resulted from reduced sociability and abnormal social information processing in Neo+ Arc/Arg3.1 KO dams, exacerbated by social communication impairments in pups. The expression of the Neo cassette product did not cause cytotoxicity, but led to altered ERK signaling, gene expression, and oxytocin system. However, oxytocin administration did not improve social impairments in Neo+ Arc/Arg3.1 KO animals. Interestingly, early social environment enrichment enhanced social interaction with familiar, but not unfamiliar conspecifics or maternal behavior. Overall, our findings reveal a major impact of the Neo cassette on behaviors, particularly social behaviors, in Arc/Arg3.1 KO mice, underscoring the need to re-examine phenotypes of animal models carrying the Neo cassette in neuroscience research.
title	The insertion of Neomycin cassette impairs maternal and social behaviors in Arc/Arg3.1 knock-out mice
topic	Neurons and Cognition
url	https://arxiv.org/abs/2505.03339