PMID- 31747920
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20211204
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 12
IP  - 1
DP  - 2019 Nov 20
TI  - Autism-like behaviors in male mice with a Pcdh19 deletion.
PG  - 95
LID - 10.1186/s13041-019-0519-3 [doi]
LID - 95
AB  - Mutations in protocadherin 19 (PCDH19), which is on the X-chromosome, cause the 
      brain disease Epilepsy in Females with Mental Retardation (EFMR). EFMR is also 
      often associated with autism-like symptoms. In mice and humans, epilepsy occurs 
      only in heterozygous females who have a mixture of PCDH19 wild-type (WT) and 
      mutant cells caused by random X-inactivation; it does not occur in hemizygous 
      PCDH19 mutant males. This unique inheritance pattern strongly suggests the 
      underlying disease mechanism operates via interference between WT and mutant 
      cells rather than being a result of complete loss of PCDH19 functions. Although 
      it remains unclear whether the other symptoms of EFMR also conform to this unique 
      genotype-phenotype relationship, PCDH19 mutant males were recently reported to 
      demonstrate autism-like symptoms. We, therefore, used a Pcdh19 knockout (KO) 
      mouse model to ask whether a complete lack of PCDH19 causes autism-like 
      behaviors. Consistent with the autism observed in EFMR females, we found Pcdh19 
      heterozygous KO female mice (with mosaic expression of PCDH19) show defects in 
      sociability in the 3-chamber test. Surprisingly, hemizygous Pcdh19 KO male mice 
      (without any PCDH19 expression) exhibit impaired sociability in the 3-chamber 
      test and reduced social interactions in the reciprocal social interaction test. 
      We also observed that, compared to WT mice, mutant mice display more repetitive 
      behaviors, including self-grooming and rearing. These findings indicate that 
      hemizygous Pcdh19 KO male mice show autism-like phenotypes.
FAU - Lim, Jisoo
AU  - Lim J
AD  - Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 03722, Korea.
FAU - Ryu, Jiin
AU  - Ryu J
AD  - Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 03722, Korea.
FAU - Kang, Shinwon
AU  - Kang S
AD  - Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 03722, Korea.
FAU - Noh, Hyun Jong
AU  - Noh HJ
AD  - Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 03722, Korea.
FAU - Kim, Chul Hoon
AU  - Kim CH
AUID- ORCID: 0000-0002-7360-429X
AD  - Department of Pharmacology, BK21 PLUS Project for Medical Science, Brain Research 
      Institute, Yonsei University College of Medicine, Seoul, 03722, Korea. 
      kimhoon@yuhs.ac.
AD  - Severance Biomedical Science Institute, Yonsei University College of Medicine, 
      Seoul, 03722, Korea. kimhoon@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191120
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (Cadherins)
RN  - 0 (Pcdh19 protein, mouse)
RN  - 0 (Protocadherins)
SB  - IM
MH  - Animals
MH  - Autistic Disorder/*genetics
MH  - *Behavior, Animal
MH  - Cadherins/*genetics
MH  - Female
MH  - *Gene Deletion
MH  - Male
MH  - Mice, Knockout
MH  - Protocadherins
MH  - Social Behavior
PMC - PMC6864969
COIS- The authors declare that they have no competing interests.
EDAT- 2019/11/22 06:00
MHDA- 2020/06/09 06:00
PMCR- 2019/11/20
CRDT- 2019/11/22 06:00
PHST- 2019/06/13 00:00 [received]
PHST- 2019/10/30 00:00 [accepted]
PHST- 2019/11/22 06:00 [entrez]
PHST- 2019/11/22 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
PHST- 2019/11/20 00:00 [pmc-release]
AID - 10.1186/s13041-019-0519-3 [pii]
AID - 519 [pii]
AID - 10.1186/s13041-019-0519-3 [doi]
PST - epublish
SO  - Mol Brain. 2019 Nov 20;12(1):95. doi: 10.1186/s13041-019-0519-3.