Abstract
The SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene encodes core scaffolds in neuronal excitatory postsynapses. SHANK3 duplications have been identified in patients with hyperkinetic disorders and early-onset generalized tonic-clonic seizures. Consistently, Shank3 transgenic (TG) mice, which mildly overexpress Shank3 proteins exhibit hyperkinetic behavior and spontaneous seizures. However, the seizure phenotype of Shank3 TG mice has only been investigated in adults of the seizure-sensitive strain FVB/N. Therefore, it remains unknown if spontaneous seizures occur in Shank3 TG mice from the early postnatal stages onward, or even in seizure-resistant strains. Clinically, generalized tonic-clonic seizures are the critical risk factor for epilepsy-associated mortality. However, the potential association between Shank3 overexpression and mortality, at least in mice, has not been investigated in detail. In the present study, we backcrossed Shank3 TG mice in seizure-resistant C57BL/6 J strain and monitored their home-cage activities at 3 weeks of age. Of the 15 Shank3 TG mice monitored, two exhibited spontaneous tonic-clonic seizures, and one died immediately after the seizure event. Based on this observation, we determined the survival rate of the Shank3 TG mice from 3 to 12 weeks of age. We found that approximately 40-45% of the Shank3 TG mice, both males and females, died before reaching 12 weeks of age. Notably, 53% and 70% of the total deaths in male and female Shank3 TG mice, respectively, occurred in the juvenile stages. These results suggest spontaneous seizure and partial lethality of juvenile Shank3 TG mice in seizure-resistant background, further supporting the validity of this model.
| Original language | English |
|---|---|
| Article number | 57 |
| Journal | Molecular Brain |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2018 Oct 10 |
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Keywords
- Juvenile stage
- Lethality
- Shank3 overexpression
- Spontaneous seizure
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
Cite this
Spontaneous seizure and partial lethality of juvenile Shank3-overexpressing mice in C57BL/6 J background. / Jin, Chunmei; Zhang, Yinhua; Kim, Shinhyun; Kim, Yoonhee; Lee, Yeunkum; Han, Kihoon.
In: Molecular Brain, Vol. 11, No. 1, 57, 10.10.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Spontaneous seizure and partial lethality of juvenile Shank3-overexpressing mice in C57BL/6 J background
AU - Jin, Chunmei
AU - Zhang, Yinhua
AU - Kim, Shinhyun
AU - Kim, Yoonhee
AU - Lee, Yeunkum
AU - Han, Kihoon
PY - 2018/10/10
Y1 - 2018/10/10
N2 - The SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene encodes core scaffolds in neuronal excitatory postsynapses. SHANK3 duplications have been identified in patients with hyperkinetic disorders and early-onset generalized tonic-clonic seizures. Consistently, Shank3 transgenic (TG) mice, which mildly overexpress Shank3 proteins exhibit hyperkinetic behavior and spontaneous seizures. However, the seizure phenotype of Shank3 TG mice has only been investigated in adults of the seizure-sensitive strain FVB/N. Therefore, it remains unknown if spontaneous seizures occur in Shank3 TG mice from the early postnatal stages onward, or even in seizure-resistant strains. Clinically, generalized tonic-clonic seizures are the critical risk factor for epilepsy-associated mortality. However, the potential association between Shank3 overexpression and mortality, at least in mice, has not been investigated in detail. In the present study, we backcrossed Shank3 TG mice in seizure-resistant C57BL/6 J strain and monitored their home-cage activities at 3 weeks of age. Of the 15 Shank3 TG mice monitored, two exhibited spontaneous tonic-clonic seizures, and one died immediately after the seizure event. Based on this observation, we determined the survival rate of the Shank3 TG mice from 3 to 12 weeks of age. We found that approximately 40-45% of the Shank3 TG mice, both males and females, died before reaching 12 weeks of age. Notably, 53% and 70% of the total deaths in male and female Shank3 TG mice, respectively, occurred in the juvenile stages. These results suggest spontaneous seizure and partial lethality of juvenile Shank3 TG mice in seizure-resistant background, further supporting the validity of this model.
AB - The SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene encodes core scaffolds in neuronal excitatory postsynapses. SHANK3 duplications have been identified in patients with hyperkinetic disorders and early-onset generalized tonic-clonic seizures. Consistently, Shank3 transgenic (TG) mice, which mildly overexpress Shank3 proteins exhibit hyperkinetic behavior and spontaneous seizures. However, the seizure phenotype of Shank3 TG mice has only been investigated in adults of the seizure-sensitive strain FVB/N. Therefore, it remains unknown if spontaneous seizures occur in Shank3 TG mice from the early postnatal stages onward, or even in seizure-resistant strains. Clinically, generalized tonic-clonic seizures are the critical risk factor for epilepsy-associated mortality. However, the potential association between Shank3 overexpression and mortality, at least in mice, has not been investigated in detail. In the present study, we backcrossed Shank3 TG mice in seizure-resistant C57BL/6 J strain and monitored their home-cage activities at 3 weeks of age. Of the 15 Shank3 TG mice monitored, two exhibited spontaneous tonic-clonic seizures, and one died immediately after the seizure event. Based on this observation, we determined the survival rate of the Shank3 TG mice from 3 to 12 weeks of age. We found that approximately 40-45% of the Shank3 TG mice, both males and females, died before reaching 12 weeks of age. Notably, 53% and 70% of the total deaths in male and female Shank3 TG mice, respectively, occurred in the juvenile stages. These results suggest spontaneous seizure and partial lethality of juvenile Shank3 TG mice in seizure-resistant background, further supporting the validity of this model.
KW - Juvenile stage
KW - Lethality
KW - Shank3 overexpression
KW - Spontaneous seizure
UR - http://www.scopus.com/inward/record.url?scp=85054776749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054776749&partnerID=8YFLogxK
U2 - 10.1186/s13041-018-0403-6
DO - 10.1186/s13041-018-0403-6
M3 - Article
C2 - 30305163
AN - SCOPUS:85054776749
VL - 11
JO - Molecular Brain
JF - Molecular Brain
SN - 1756-6606
IS - 1
M1 - 57
ER -