Contactin‑associated protein‑like 2 expression in SH‑SY5Y cells is upregulated by a FOXP2 mutant with a shortened poly‑glutamine tract.
The forkhead box protein P2 (FOXP2) gene encodes an important transcription factor that contains a polyglutamine (poly‑Q) tract and a forkhead DNA binding domain. It has been observed that FOXP2 is associated with speech sound disorder (SSD), and mutations that decrease the length of the poly‑Q tract were identified in the FOXP2 gene of SSD patients. However, the exact role of poly‑Q reduction is not well understood. In the present study, constructs expressing wild‑type and poly‑Q reduction mutants of FOXP2 were generated by polymerase chain reaction (PCR) using lentiviral vectors and transfected into the SH‑SY5Y neuronal cell line. Quantitative reverse transcription (qRT)‑PCR and western blotting indicated that infected cells stably expressed high levels of FOXP2. Using this cell model, the impact of FOXP2 on the expression of contactin‑associated protein‑like 2 (CNTNAP2) were investigated, and CNTNAP2 mRNA expression levels were observed to be significantly higher in cells expressing poly‑Q‑reduced FOXP2. In addition, the expression level of CASPR2, a mammalian homolog of Drosophila Neurexin IV, was increased in cells expressing the FOXP2 mutant. Demonstration of regulation by FOXP2 indicates that CNTNAP2 may also be involved in SSD.
Department of Developmental Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Yunjing
Y
Zhao
Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Xiaoliang
X
Liu
Department of Pediatrics, Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.
Hongwei
H
Sun
Department of Clinical Genetics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Yueping
Y
Wang
Department of Developmental Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Wenzhu
W
Yang
Department of Developmental Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
Hongwei
H
Ma
D001483:Base Sequence; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005973:Glutamine / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics; D066229:Speech Sound Disorder / Q000235:genetics; D015854:Up-Regulation
C403049:CNTNAP2 protein, human; C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D005973:Glutamine; C097188:polyglutamine