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CABP4 mutation in mice shows alteration in protein expression level and neuron discharge frequency.
Shi, Gang-An; Liang, Ming-Juan; Miao, Qin-Fei; Li, Xue-Ping; Qiu, Wei-Feng; Zeng, Tian-Qian; Zhai, Qiong-Xiang; Chen, Zhi-Hong.
Afiliación
  • Shi GA; School of Medicine, South China University of Technology, Guangzhou, China.
  • Liang MJ; Department of Pediatrics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Miao QF; Department of Pediatrics, Foshan Maternity & Child Healthcare Hospital, Foshan, China.
  • Li XP; Department of Neurology Rehabilitation, Guangdong Maternal and Child Hospital, Guangzhou, China.
  • Qiu WF; Department of Pediatrics, Foshan Maternity & Child Healthcare Hospital, Foshan, China.
  • Zeng TQ; Department of Pediatrics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
  • Zhai QX; School of Medicine, University of Shantou, Shantou, China.
  • Chen ZH; Department of Pediatrics, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Transl Pediatr ; 13(5): 705-715, 2024 May 31.
Article en En | MEDLINE | ID: mdl-38840676
ABSTRACT

Background:

The calcium-binding protein 4 (CABP4) gene is a newly identified epilepsy-related gene that might be associated with a rare type of genetic focal epilepsy; that is, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). In vitro, mutant CABP4 causes an increased inward flow voltage of calcium ions and a significant increase in the electrical signal discharge in hippocampus neurons; however, the role of CABP4 in epilepsy has not yet been specifically described, and there is not yet a CABP4 mutant animal model recapitulating the epilepsy phenotype.

Methods:

We introduced a human CABP4 missense mutation into the C57BL/6J mouse genome and generated a knock-in strain carrying a glycine-to-aspartic acid mutation in the gene. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to evaluate the CABP4 expression level. Slice patch-clamp recording was carried out on pyramidal cells of prefrontal cortex layers II and III.

Results:

The CABP4G155D/+ mutant mice were viable and born at an expected Mendelian ratio. Surprisingly, the heterozygous (HE) mice did not display either an abnormal appearance or an overt seizure phenotype, and there was no statistically significant difference between the HE and wild-type (WT) mice in terms of overall messenger RNA (mRNA) and protein expression. However, the HE mutant mice showed an imbalance in the amount of protein expressed in the brain regions. Additionally, the patch-clamp recordings from the HE mouse layer II/III cortical pyramidal cells revealed an increase in the frequency of micro-excitatory post-synaptic currents (mEPSCs) but no change in the amplitude was observed.

Conclusions:

The findings of this study suggest that the CABP4 p.G155D mutation might be one of the mechanisms underlying seizure onset.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Pediatr Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Pediatr Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China