Rat embryonic stem cells create new era in development of genetically manipulated rat models

Table 1 Summary of components for the establishment of rat embryonic stem cells and the properties of the resultant cells

Ref.	Additives	Pluripotent markers	Karyotype stability	EB/teratocarcinoma	Germline transmission
Iannacconne et al[13]	FBS	AP	Unconfirmed	Failed	Failed
	LIF	SSEA1
Takahama et al[14]	FBS	AP	Unconfirmed	Unconfirmed	Unconfirmed
	LIF	Oct3/4
		SSEA1
Vassilieva et al[15]	FBS	AP	Unconfirmed	Unconfirmed	Unconfirmed
	LIF	Oct3/4
		SSEA1
Buehr et al[9]	(A) N2B27		Confirmed	Confirmed	Confirmed
	FGFRi	AP
	MEKi	Oct3/4
	GSK3i	SSEA1
	(B)	Sox2
	N2B27
	MEKi	Nanog
	GSK3i	Fgf4
	LIF	Rex1
Li et al[10]	(A) N2B27		Confirmed	Confirmed	Confirmed
	MEKi	AP
	GSK3i	Oct3/4
	(B)	SSEA1
	N2B27
	MEKi	Sox2
	GSK3i	Nanog
	LIF
Kawamata et al[26]	FBS	AP	Confirmed	Confirmed	Confirmed
	MEKi	Oct3/4
	GSK3i	Sox2
	ALK5i	Nanog
	ROCKi	Rex1

EB: Embryo culture media; FBS: Fetal bovine serum; LIF: Leukemia inhibitory factor; MEK: Mitogen-activated protein kinase/ERK kinase; GSK3: Glycogen synthase kinase 3; FGFR: Fibroblast growth factor-receptor; ALK5: Activin receptor-like kinase; ROCK: Rho-associated, coiled-coil containing protein kinase; AP: Alkaline phosphatase.

Table 2 List of knock-out rats generated using new gene-targeted technologies and rat embryonic stem cell-based technologies

Ref.	Cell type	Technology	Target
Ménoret et al[69]	Embryo	Meganuclease	Rag1
Ménoret et al[70]	Embryo	ZFN	Immunoglobulin heavy chain
Zschemisch et al[71]	Embryo	ZFN	Rag1
Geurts et al[7]	Embryo	ZFN	GFP
	Embryo	ZFN	IgM
	Embryo	ZFN	Rab38
Mashimo et al[8]	Embryo	ZFN	IL-2 receptor gamma
Moreno et al[72]	Embryo	ZFN	Renin
Chu et al[73]	Embryo	ZFN	Mdr1
Vaira et al[74]	Embryo	ZFN	Reptin
Tesson et al[66]	Embryo	TALEN	IgM
Ferguson et al[67]	Embryo	TALEN	Tlr4
Yamamoto et al[48]	ES cells	Homologous Recombination	Par2
Tong et al[11]	ES cells	Homologous Recombination	p53
Kawamata et al[52]	ES cells	ZFN	p53

ES: Embryonic stem; ZFN: Zinc-finger nuclease; TALEN: Transcription activator-like effector nuclease.