B6(Cg)-Tet1^tm1Koh/Orl

Status	Available to order
EMMA ID	EM:15880
Citation information	RRID:IMSR_EM:15880 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information.
International strain name	B6(Cg)-Tet1^tm1Koh/Orl
Alternative name	C57BL/6-Tet1 tm1Koh
Strain type	Targeted Mutant Strains : Knock-in
Allele/Transgene symbol	Tet1^tm1Koh
Gene/Transgene symbol	Tet1

Information from provider

Provider	Kian Koh
Provider affiliation	KU Leuven
Genetic information	A targeting vector was designed to insert an “fl-NLS-lacZ-fl-mCherry-FRT-neo-FRT” cassette in-frame at the ATG start codon in exon 2 of the Tet1 gene. The targeting vector contains an ATG start codon and nuclear localization signal sequence 5’ of lacZ reporter gene with 3’ BGH polyA, flanked by 2 LoxP sites to allow reporter exchange to a downstream ATG-mCherry-pA cassette by cre recombination, followed by a FRT-flanked neomycin selection cassette. The targeting construct was electroporated into C57BL/6 mouse embryonic stem (ES) cells and selected in G418. The targeted knock-in mouse strain was created by blastocyst injection of one correctly targeted clone. The strain has been bred to flp-deleter mice to remove the neo cassette, resulting in one remaining FRT site downstream of the fl-NLS-lacZ-fl-mCherry cassette. The final modification is designated as Tet1-fl-lacZ-fl-mCherry.
Phenotypic information	Homozygous: Tet1 null mice display partially penetrant embryonic lethality. In B6 strains, some Tet1 null mice (~30% of KOs) survive to birth with very mild developmental defects – reported as small size and cognitive disorders. However, roughly two-thirds of KOs are embryonic lethal by E9.5. In CD1 outbred stocks, >70% of KOs are embryonic lethal from cranial neural tube defects (exencephaly) manisfesting from E9.5 until E13.5 (end point of all timed pregnancies). Intercrosses of Tet1tm1Koh heterozygous mice are producing small litters (typically 2-4 pups) compared to het x wt matings (typically 6-8 pups). Heterozygous: All heterozygous mice are normal when fed regular chow diet. When heterzygous dams are fed folic acid-depleted custom diet for 4 weeks prior to timed pregnancies, rare cases (6.5%) of cranial neural tube defects are observed in heterozygous offspring by E11.5.
Breeding history	The gene targeted knock-in/knock-out mouse strain was created at Ozgene Pte Ltd (Australia) in a C57BL/6J congenic background using goGermline technology by blastocyst injection of one correctly targeted ES cell clone. As stated above, the strain has been bred to flp-deleter mice to remove the neo cassette upon delivery to Leuven. The strain was cryopreserved after one generation of backcrossing to C57BL/6J at KU Leuven. Currently live colonies of heterozygous mice have been backcrossed for 7 generations to C57BL/6J.
References	Lineage-specific functions of TET1 in the postimplantation mouse embryo.;Khoueiry Rita, Sohni Abhishek, Thienpont Bernard, Luo Xinlong, Velde Joris Vande, Bartoccetti Michela, Boeckx Bram, Zwijsen An, Rao Anjana, Lambrechts Diether, Koh Kian Peng, ;2017;Nature genetics;49;1061-1072; 28504700 Regulatory Dynamics of Tet1 and Oct4 Resolve Stages of Global DNA Demethylation and Transcriptomic Changes in Reprogramming.;Bartoccetti Michela, van der Veer Bernard K, Luo Xinlong, Khoueiry Rita, She Pinyi, Bajaj Manmohan, Xu Jiayi, Janiszewski Adrian, Thienpont Bernard, Pasque Vincent, Koh Kian Peng, ;2020;Cell reports;30;2150-2169.e9; 32075734 Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation.;van der Veer Bernard K, Chen Lehua, Custers Colin, Athanasouli Paraskevi, Schroiff Mariana, Cornelis Riet, Chui Jonathan Sai-Hong, Finnell Richard H, Lluis Frederic, Koh Kian Peng, ;2023;Nucleic acids research;51;5469-5498; 37021585 Coordination of germ layer lineage choice by TET1 during primed pluripotency.;Luo Xinlong, van der Veer Bernard K, Sun Lei, Bartoccetti Michela, Boretto Matteo, Vankelecom Hugo, Khoueiry Rita, Koh Kian Peng, ;2020;Genes & development;34;598-618; 32115407 The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.;Chen Lehua, van der Veer Bernard K, Chen Qiuying, Champeris Tsaniras Spyridon, Brangers Wannes, Kwak Harm H M, Khoueiry Rita, Lei Yunping, Cabrera Robert, Gross Steven S, Finnell Richard H, Koh Kian Peng, ;2025;EMBO reports;26;175-199; 39578553
Homozygous fertile	no
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	CNRS-TAAM – Typing and Archiving of Animal Models, Orléans, France

Disease and phenotype information

MGI phenotypes (gene matching)

midline facial cleft / MGI
decreased neutrophil cell number / MGI
irregular coat pigmentation / MGI
abnormal lateral ventricle morphology / MGI
incomplete rostral neuropore closure / MGI
small ovary / MGI
decreased body length / MGI
decreased body weight / MGI
decreased body size / MGI
ocular hypertelorism / MGI
abnormal temporal memory / MGI
abnormal embryo development / MGI
anencephaly / MGI
decreased litter size / MGI
abnormal forebrain development / MGI
absent ovary / MGI
nervous system phenotype / MGI
abnormal female reproductive system physiology / MGI
abnormal neural tube closure / MGI
embryonic growth retardation / MGI
decreased ovary weight / MGI
abnormal female meiosis / MGI
reproductive system phenotype / MGI
decreased oocyte number / MGI
abnormal interfrontal bone morphology / MGI
abnormal paraventricular hypothalamic nucleus morphology / MGI
abnormal supraoptic nucleus morphology / MGI
abnormal synaptonemal complex / MGI
decreased birth body size / MGI
increased lipoma incidence / MGI
abnormal double-strand DNA break repair / MGI
embryonic lethality, complete penetrance / MGI
embryonic lethality during organogenesis, complete penetrance / MGI
preweaning lethality, complete penetrance / MGI
prenatal lethality, incomplete penetrance / MGI
excessive folding of visceral yolk sac / MGI
abnormal head fold morphology / MGI
encephalomeningocele / MGI
impaired spatial learning / MGI
abnormal lamina terminalis morphology / MGI
bifid nose / MGI

Literature references

Lineage-specific functions of TET1 in the postimplantation mouse embryo.;Khoueiry Rita, Sohni Abhishek, Thienpont Bernard, Luo Xinlong, Velde Joris Vande, Bartoccetti Michela, Boeckx Bram, Zwijsen An, Rao Anjana, Lambrechts Diether, Koh Kian Peng, ;2017;Nature genetics;49;1061-1072; 28504700
Regulatory Dynamics of Tet1 and Oct4 Resolve Stages of Global DNA Demethylation and Transcriptomic Changes in Reprogramming.;Bartoccetti Michela, van der Veer Bernard K, Luo Xinlong, Khoueiry Rita, She Pinyi, Bajaj Manmohan, Xu Jiayi, Janiszewski Adrian, Thienpont Bernard, Pasque Vincent, Koh Kian Peng, ;2020;Cell reports;30;2150-2169.e9; 32075734
Dual functions of TET1 in germ layer lineage bifurcation distinguished by genomic context and dependence on 5-methylcytosine oxidation.;van der Veer Bernard K, Chen Lehua, Custers Colin, Athanasouli Paraskevi, Schroiff Mariana, Cornelis Riet, Chui Jonathan Sai-Hong, Finnell Richard H, Lluis Frederic, Koh Kian Peng, ;2023;Nucleic acids research;51;5469-5498; 37021585
Coordination of germ layer lineage choice by TET1 during primed pluripotency.;Luo Xinlong, van der Veer Bernard K, Sun Lei, Bartoccetti Michela, Boretto Matteo, Vankelecom Hugo, Khoueiry Rita, Koh Kian Peng, ;2020;Genes & development;34;598-618; 32115407
The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.;Chen Lehua, van der Veer Bernard K, Chen Qiuying, Champeris Tsaniras Spyridon, Brangers Wannes, Kwak Harm H M, Khoueiry Rita, Lei Yunping, Cabrera Robert, Gross Steven S, Finnell Richard H, Koh Kian Peng, ;2025;EMBO reports;26;175-199; 39578553

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B6(Cg)-Tet1tm1Koh/Orl