. 2017 Jul 18;38(4):171–179. doi: 10.24272/j.issn.2095-8137.2017.042

1.

SRS in transgenic models of epilepsy

Gene	Modification	Latency	Frequency and features of SRS	References
^*: model or strain dependent phenotype; ECS: editing site complementary sequence; OE: overexpression; SRS: spontaneous recurrent seizures; SUDEP: sudden unexpected death in epilepsy; SWD: spike-wave discharges.
Scn1a	Scn1a^-/-	P9	Generalized convulsive SRS. SUDEP at P15	Yu et al., 2006
	Scn1a^+/-	P21–P27	EEG and/or behavioral SRS lasted 20 s. Sporadic SUDEP from P21^*
	Scn1a^Flox/+:: Zp3-Cre^+/-	N/A	12 out of 23 mice exhibited behavioral SRS (3 times/day, lasted 35 s). Lifespan of P33	Dutton et al., 2013
	Scn1a^Flox/+:: Ppp1r2-Cre^+/-	N/A	2 out of 6 mice exhibited behavioral and/or EEG SRS
	Scn1a^{R1407X/R1407X}	P12–P16	Multiple tonic-clonic SRS/day confirmed by EEG (lasted 1–3 min, interval: 1–4 hr). SUDEP by P21	Ogiwara et al., 2007
	Scn1a^R1407X/+	P18	Sporadic SUDEP in 1–3 mo^*
	Scn1a^{R1648H/R1648H}	P16	Behavioral SRS lasted 30–90 s. SUDEP P16–P26	Martin et al., 2010
	Scn1a^R1648H/+	N/A	2 out of 14 mice exhibited 21 SRS in total during 96 h EEG recording
Scn2a	Scn2a^Q54	2 mo^*	EEG and behavioral SRS. Frequency and duration of SRS increased with age^*	Kearney et al., 2001
Scn8a	Scn8a^8J/+, Scn8a^med/+ or Scn8a^med-jo/+	N/A	SWD with behavioral arrest^*	Papale et al., 2009
	Scn8^{N1768D/N1768D}	3 wk	No SRS prior to day of SUDEP 3 wk. SRS lasted <1 min	Wagnon et al., 2015
	Scn8^N1768D/+	8–16 wk	0–3 SRS/day. SRS lasted <1 min. SUDEP 14 wk
	Scn8^N1768D/-	8 wk	As many as 25 SRS/day. SUDEP 9 wk
Scn1b	Scn1b^-/- or Scn1b^del/del	P10	EEG and behavioral SRS at random intervals with duration from seconds to minutes. SUDEP 3 wk	Chen et al., 2004; 2007
Kcnq2	Kcnq2^A306T/A306T	P24	Generalized EEG and behavioral SRS. SUDEP P16–P32^*	Singh et al., 2008
Kcnq3	Kcnq3^G311V/G311V	2 wk	Generalized EEG and behavioral SRS. SUDEP P0–P73^*	Singh et al., 2008
Kcna1	Kcna1^-/-	3 wk	Behavioral SRS lasted 20 s–2 min once or twice/hr throughout adult life. SUDEP 3–5 wk	Smart et al., 1998
Kcna2	Kcna2^-/-	N/A	Tonic-clonic SRS. SUDEP at P17	Brew et al., 2007; Douglas et al., 2007
Kcnmb4	Kcnmb4^-/-	N/A	Generalized EEG seizures without overt behavioral manifestation	Brenner et al., 2005
Cacna1a	Deletion (α_1A^−/−)	N/A	Absence seizures. SUDEP 3–4 wk	Jun et al., 1999
Gria2	Gria2^+/ΔECS	P12	Behavioral SRS (once/4 hr). SUDEP by P20	Brusa et al., 1995
Chrna4	Chrna4^{S252F/S252F or +} and Chrna4^{+L264/+L264 or +}	N/A	SRS with high-amplitude, low-frequency cortical EEG activity, prominent theta and delta waves	Klaassen et al., 2006
Gabrg2	Gabrg2^+/- or Gabrg2^+/R43Q	P20	Behavioral arrest and associated SWD^* (up to 50 times/hr and variable)	Reid et al., 2013; Tan et al., 2007
Tsc1/2	Tsc1/2^flox/flox::GFAP-Cre	2–3 wk	Generalized tonic-clonic SRS. Few SRS at 3 wk, frequency increased over time. SUDEP 7–10 wk	Zeng et al., 2011
Fgf13	Fgf13^+/-	P15	Behavioral and EEG SRS. Frequency and duration varied by animal	Puranam et al., 2015
Lgi1	Lgi1^-/-	P10	Clonic SRS (1.6 seizures/hr at P14). SUDEP at P20	Chabrol et al., 2010
BACE1	BACE1^-/-	N/A	<40% rats exhibited generalized SRS and/or absence seizures	Hitt et al., 2010
APP	APdE9	N/A	65% exhibited SRS, 10%–15% mortality at any age but peak around 3–4 mo	Minkeviciene et al., 2009
APP	hAPP_FAD	N/A	Spontaneous nonconvulsive seizure activity. Occurrence of SUDEP	Palop et al., 2007
Ube3a	Ube3a^m+/p-	P18	SWD accompanied by behavioral immobility or tonic-clonic SRS^*	Miura et al., 2002, Jiang et al., 1998a; 2010
Mecp2	Viaat-Mecp2^−/y Mecp2^308/y	5 wk N/A	Spontaneous rhythmic EEG activity including SWD^* Spontaneous behavioral myoclonic jerks	Chao et al., 2010 D'Cruz et al., 2010
Shank3	Shank3 OE	N/A	Hyperexcitability discharges accompanied by EEG SRS	Han et al., 2013
CNTNAP2	CNTNAP2^-/-	6 mo	SRS with generalized interictal spike discharges	Peñagarikano et al., 2011
Epm2A	Epm2A^-/-	<9 mo	80% exhibited myoclonic SRS, more frequent during dark cycle	Ganesh et al., 2002
Celf4	Celf4^Ff/Ff or Celf4^Ff/+	3 mo	Recurrent tonic-clonic seizures or absence seizures^*	Yang et al., 2007
Map2k1	caMEK1^flox/flox::Nestin-Cre	6–8 wk	Lifetime behavioral arrest and forelimb myoclonus (6.2 SRS/7 hr)	Nateri et al., 2007