Table 3.

Summary of the behavioral phenotypes and comparison of the different lines of Nrg1-related mutant mice.

Genetic mouse model for	Behavioral phenotype
	Learning and memory	Sensorimotor gating and information processing	Social	Motor function and locomotor activity	Explorative behavior	Anxiety-like behavior	Hedonia
TM domain (exon 9, the novel TMc-Nrg1 mutant mice)	Object recognition ♂ ↓	PPI =	Preference =	OF =	HB =	EPM =	Sucrose =
	Contextual FC ♂ ↓		Recognition =	HB =	EPM =
	Cued FC ♂ ↓
	WMW =
Background:
C57BL/6
TM domain (exon 11, the original TMc-Nrg1 mutant mice)	Object recognition ↓	PPI =	Preference =	OF ↑	Explorative behavior ↑	OF =	Sucrose =
	Contextual FC ↓	(Boucher et al., 2007)	Recognition ↓	(Stefansson et al., 2002)	♀ (O'Tuathaigh et al., 2006)	(Boucher et al., 2007)	(Desbonnet et al., 2012)
	Passive avoidance =	(Van Den Buuse et al., 2009)	(O'Tuathaigh et al., 2007)	♂ ♀ (O'Tuathaigh et al., 2006)		OF ↓ (PND138; 60)
	(Duffy et al., 2010)	PPI ↓	(Desbonnet et al., 2012)	(Boucher et al., 2007)	HB ↑	(Karl et al., 2007)
Background:	♀ (Chesworth et al., 2012)	(Stefansson et al., 2002)	Interaction =	PND 138	LD ↑ (vertical activity)	(Desbonnet et al., 2012)
C57BL/6	Cued FC =	(Desbonnet et al., 2012)	(Boucher et al., 2007)	(Karl et al., 2007)	(Boucher et al., 2007)	EPM ↓
	(Duffy et al., 2010)		(Desbonnet et al., 2012)	15-week-old	(Karl et al., 2007)	LD ↑
	Cued FC ↓	Startle =	Aggression ↑	♀ (Chesworth et al., 2012)	LD =	(Boucher et al., 2007)
	♀ (Chesworth et al., 2012)	(Boucher et al., 2007)	♂ ♀ (O'Tuathaigh et al., 2007)	3-month-old	(Karl et al., 2007)
	Radial arm maze =	Startle ↓	(O'Tuathaigh et al., 2008)	(Van Den Buuse et al., 2009)		EPM =
	(Duffy et al., 2010)	(Desbonnet et al., 2012)	Aggression =	OF =		LD =
	Y-maze =		Agonistic behavior ↑	PND 91		(Karl et al., 2007)
	♂ ♀ (O'Tuathaigh et al., 2007)		(Desbonnet et al., 2012)	(Karl et al., 2007)		(O'Tuathaigh et al., 2008)
	(Duffy et al., 2010)		Agonistic behavior =	7–8-month-old
	♀ (Desbonnet et al., 2012)		(Boucher et al., 2007)	(Van Den Buuse et al., 2009)
	Barnes maze ↓		(O'Tuathaigh et al., 2008)
	♂ (O'Tuathaigh et al., 2007)
	Cheeseboard =
	♀ (Chesworth et al., 2012)
EGF-like Domain (exon 6)	Contextual FC ↓	PPI =	Recognition ↓	OF ↑	HB =	OF ↓
	Object recognition =	(Duffy et al., 2008)	(Ehrlichman et al., 2009)	LD ↑	(Duffy et al., 2008)	EPM =
	(Ehrlichman et al., 2009)	(Ehrlichman et al., 2009)		Marble burying =		LD =
Background:
C57BL/6
(Duffy et al., 2008)
	Cross maze =	MMN ↓		(Duffy et al., 2008)		(Duffy et al., 2008)
	(Duffy et al., 2008)	P20 =		OF =
		P40 =		(Ehrlichman et al., 2009)
		(Ehrlichman et al., 2009)		Bar test =
C57BL/6 × 129/SVEV				Rotard rod =
				(Michailov et al., 2004)
(Ehrlichman et al., 2009)
Ig-like domain (exon 3)	T maze =			Running wheel =
	Latent inhibition ↓ (Rimer et al., 2005)			(Rimer et al., 2005)
Background:
C57BL/6
Type III	DNMS ↓	PPI ↓		OF =
Background:	(Chen et al., 2008)	(Chen et al., 2008)		(Chen et al., 2008)
C57BL/6
ErbB4+/−		PPI =		OF ↑
Background:		(Stefansson et al., 2002)		(Stefansson et al., 2002)
C57BL/6
CNS-specific ErbB4 KO	MWM			OF ↓ delayed motor development (Golub et al., 2004)
	♂ ↓ (Golub et al., 2004)
Background:
C57BL/6
Heart-rescued ErbB4 KO	Cued FC ↓	PPI ↓		OF ↓		EPM ↓
	Contextual FC ↓	(Shamir et al., 2012)		(Shamir et al., 2012)		(Shamir et al., 2012)
	(Shamir et al., 2012)
Background:
C57BL/6
PV-Cre; ErbB4	Cued FC =	PPI ↓		OF ↑		EPM =
	Contextual FC =	(Shamir et al., 2012)		(Shamir et al., 2012)		(Shamir et al., 2012)
Background:	(Shamir et al., 2012)
C57BL/6 × 129/SVEV	Radial arm maze ↓
	(Wen et al., 2010)
CNS-specific
ErbB2/4 KO
Background:
FVB		PPI ↓	Aggressive ↑			OF ↓
		(Barros et al., 2009)	(Barros et al., 2009)			(Barros et al., 2009)
Transgenic NRG1	Contextual FC ↓	PPI ↓	Interaction ↑	OF ↑ (Kato et al., 2010)
	Cued FC =	(Kato et al., 2010)	Aggression ↑
Background: not described	(Kato et al., 2010)		(Kato et al., 2010)
Transgenic	Y-maze = (11 month)	%PPI ↓		OF = (5, 7.5, 10 month)
Type I	DNMS = (3 month)	ASR ↑		OF ↑ (12.5 month)
Background:	DNMS ↓ (10 month)	(Deakin et al., 2012)		(Deakin et al., 2012)
C57BL/6	(Deakin et al., 2012)			Rotard rod =
				(Michailov et al., 2004)
				Rotard rod ↓
				Nesting ↓
				Burrowing ↓
				(Deakin et al., 2009)

A comparison of the behavioral phenotypes of different mutants (left column, from top to bottom), including the novel TMc- Nrg1^+/− mutant mice, the original TMc-Nrg1^+/− mutant mice, Nrg1 heterozygous knockout mice with an EFG-like domain truncation of exon 6, Nrg1 heterozygous knockout mice with an Ig-like domain truncation (type I and II) of exon 3, Type III (CRD-domain) Nrg1 mutant mice, ErbB4 mutant mice, CNS-specific ErbB4 knock-out mice, ErbB4 knock-out mice that were rescued from embryonic lethality by reexpression of ErbB4 in the heart, parvalbumin-positive-specific ErbB4 knock-out mice, CNS-specific ErbB2/4 knock-out mice, Nrg1 overexpression transgenic mice, and type I Nrg1 overexpression transgenic mice. All studies summarized in this table were conducted in only male Nrg1-related mice except one study used only female mice and two studies used both male and female mice. Among these 3 studies, ♂ indicates that only male (but not female) mutants showed behavioral deficits, and ♀ indicates that only female (but not male) mutants showed behavioral impairments. Behavioral phenotypes are divided based on tasks (top row, from left to right) into categories that include learning and memory, sensorimotor gating, information processing, social function, motor function and locomotor activity, explorative behavior, anxiety-like behavior, and hedonia. NORT, novel object recognition task; FC, fear conditioning task; MWM, Morris water maze; DNMS, delay non-match to sample tasks; PPI, prepulse inhibition; ASR, auditory brain response; startle, startle response; MMN, mismatch negativity; P20, P20 event-related potential (ERP); P40, P40 ERP; OF, open field task; LD, light-dark chamber task; HB, hole broad task; EPM, elevated plus maze task; sucrose, sucrose preference task; ↑, increased in mutant mice compared to wild type littermates; ↓, decreased in mutant mice compared to wild type littermates; =, no difference between mutant mice and wild type littermates.