The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity

Nora Bourbia; Paige Chandler; Gemma Codner; Gareth Banks; Patrick M. Nolan

doi:10.1007/s00335-019-09800-9

The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity

Nora Bourbia
, Paige Chandler
, Gemma Codner
, Gareth Banks
, Patrick M. Nolan^*

^*Corresponding author for this work

Radiation Effects

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a Spata13 knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that Spata13 modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light–dark cycle. In summary, Spata13 modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.

Original language	English
Pages (from-to)	54-62
Number of pages	9
Journal	Mammalian Genome
Volume	30
Issue number	3-4
DOIs	https://doi.org/10.1007/s00335-019-09800-9
Publication status	Published - 1 Apr 2019

Bibliographical note

Funding Information:
Acknowledgements We would like to thank the staff of the Mary Lyon Centre for the maintenance and welfare of mouse lines and the Molecular and Cellular Biology group for generating Spata13 KO mice. This work was supported by the Medical Research Council (Grant Code MC_U142684173).

Funding Information:
All animal work was performed under the guidance issued by the Medical Research Council and Home Office Project License 30/3206, with local ethical approval. Mice were bred in the Mary Lyon Centre at the MRC Harwell Institute and, when not undergoing phenotyping, were kept in mixed-genotype groups in a 12 h light dark cycle (lights on at 07:00; lights off at 19:00) with ad libitum food and water.

Publisher Copyright:
© 2019, The Author(s).

Access to Document

10.1007/s00335-019-09800-9

Cite this

@article{e2e10f2be19d4517911dfa236b4266ce,

title = "The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity",

abstract = "Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a Spata13 knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that Spata13 modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light–dark cycle. In summary, Spata13 modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.",

author = "Nora Bourbia and Paige Chandler and Gemma Codner and Gareth Banks and Nolan, \{Patrick M.\}",

note = "Funding Information: Acknowledgements We would like to thank the staff of the Mary Lyon Centre for the maintenance and welfare of mouse lines and the Molecular and Cellular Biology group for generating Spata13 KO mice. This work was supported by the Medical Research Council (Grant Code MC\_U142684173). Funding Information: All animal work was performed under the guidance issued by the Medical Research Council and Home Office Project License 30/3206, with local ethical approval. Mice were bred in the Mary Lyon Centre at the MRC Harwell Institute and, when not undergoing phenotyping, were kept in mixed-genotype groups in a 12 h light dark cycle (lights on at 07:00; lights off at 19:00) with ad libitum food and water. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = apr,

day = "1",

doi = "10.1007/s00335-019-09800-9",

language = "English",

volume = "30",

pages = "54--62",

journal = "Mammalian Genome",

issn = "0938-8990",

publisher = "Springer",

number = "3-4",

}

TY - JOUR

T1 - The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity

AU - Bourbia, Nora

AU - Chandler, Paige

AU - Codner, Gemma

AU - Banks, Gareth

AU - Nolan, Patrick M.

N1 - Funding Information: Acknowledgements We would like to thank the staff of the Mary Lyon Centre for the maintenance and welfare of mouse lines and the Molecular and Cellular Biology group for generating Spata13 KO mice. This work was supported by the Medical Research Council (Grant Code MC_U142684173). Funding Information: All animal work was performed under the guidance issued by the Medical Research Council and Home Office Project License 30/3206, with local ethical approval. Mice were bred in the Mary Lyon Centre at the MRC Harwell Institute and, when not undergoing phenotyping, were kept in mixed-genotype groups in a 12 h light dark cycle (lights on at 07:00; lights off at 19:00) with ad libitum food and water. Publisher Copyright: © 2019, The Author(s).

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a Spata13 knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that Spata13 modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light–dark cycle. In summary, Spata13 modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.

AB - Spermatogenesis-associated protein 13 (Spata13) is a guanine nucleotide exchange factor (GEF) enriched in discrete brain regions in the adult, with pronounced expression in the extended central amygdala (CeA). Loss of Spata13, also known as the adenomatous polyposis coli exchange factor Asef2, has no identifiable phenotype although it has been shown to reduce the number and size of intestinal tumours in Apc (Min/+) mice. Nevertheless, its brain-related functions have not been investigated. To pursue this, we have generated a Spata13 knockout mouse line using CRISPR-mediated deletion of an exon containing the GTPase domain that is common to multiple isoforms. Homozygous mutants were viable and appeared normal. We subjected both male and female cohorts to a comprehensive battery of behavioural tests designed to investigate particular CeA-related functions. Here, we show that Spata13 modulates social behaviour with homozygous mutants being subordinate to wildtype controls. Furthermore, female homozygotes show increased activity in home cages during the dark phase of the light–dark cycle. In summary, Spata13 modulates social hierarchy in both male and female mice in addition to affecting voluntary activity in females.

UR - https://www.scopus.com/pages/publications/85064756915

U2 - 10.1007/s00335-019-09800-9

DO - 10.1007/s00335-019-09800-9

M3 - Article

C2 - 31020388

AN - SCOPUS:85064756915

SN - 0938-8990

VL - 30

SP - 54

EP - 62

JO - Mammalian Genome

JF - Mammalian Genome

IS - 3-4

ER -

The guanine nucleotide exchange factor, Spata13, influences social behaviour and nocturnal activity

Abstract

Bibliographical note

Access to Document

Other files and links

Fingerprint

Cite this