Disregulation of Autophagy in the Transgenerational Cc2d1a Mouse Model of Autism

  • Halime Dana
  • Keziban Korkmaz Bayramov
  • Nesrin Delibaşı
  • Reyhan Tahtasakal
  • Ruslan Bayramov
  • Zuhal Hamurcu
  • Elif Funda SenerEmail author
Original Paper


Autism spectrum disorder (ASD) is a heterogeneously childhood neurodevelopmental disorder, believed to be under development of various genetic and environmental factors. Autophagy and related pathways have also been implicated in the etiology of ASD. We aimed to investigate autophagic markers by generating the transgenerational inheritance of ASD-like behaviors in the Cc2d1a animal model of ASD. Cc2d1a (+/−) mouse model of ASD was built in two different groups by following three generations. After behavior test, bilateral hippocampus was sliced. Western Blot assay and quantitative real-time polymerase chain reaction (QRT-PCR) were used for measurement of LC3 and Beclin-1 as key regulators of autophagy. All of the animal and laboratory studies were conducted in the Erciyes University Genome and Stem Cell Center (GENKOK). Significant LC3 and Beclin-1 mRNA expression levels were observed in mouse hippocampus between groups and generations. Western blot confirmed the changes of the proteins in the hippocampus. LC3 expressions were increased for females and decreased for males compared to the control group. Beclin-1 expression levels were found to be significantly decreased in males and females compared to controls. This study could help explain a new pathway of autophagy in ASD mouse models. Future animal studies need to investigate sex differences in mouse modeling autism-relevant genes like CC2D1A. We anticipate our results to be a starting point for more comprehensive autophagy studies in this mouse model of ASD.


Autism CC2D1A Hippocampus Autophagy LC3 Beclin-1 



The authors are grateful to Prof. Dr. Minoo Rassoulzadegan for her advice on mouse line generation and critics for the draft. Work in our laboratory is supported by Research Fund of the Erciyes University (Project Number: TYL-2016-6347).

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest or other disclosures to report.

Supplementary material

12017_2019_8579_MOESM1_ESM.docx (222 kb)
Supplementary material 1 (DOCX 221 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical Biology, Medical FacultyErciyes UniversityKayseriTurkey
  2. 2.Genome and Stem Cell Center (GENKOK)Erciyes UniversityKayseriTurkey
  3. 3.Department of Medical GeneticsHaseki Education Research HospitalIstanbulTurkey

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