IMPC phenotypes (gene matching)
- abnormal posture / IMPC
B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze Tg(Gad2-Ncre/ERT2)1Jhi Tg(Slc6a5-ERT2/Ccre)1Jhi/Ph
| Status | Available to order |
| EMMA ID | EM:12608 |
| International strain name | B6.Cg-Gt(ROSA)26Sortm14(CAG-tdTomato)Hze Tg(Gad2-Ncre/ERT2)1Jhi Tg(Slc6a5-ERT2/Ccre)1Jhi/Ph |
| Alternative name | COTRIND [Gad2-NCreERT2 x Slc6a5-ERT2CCre x Ai14] |
| Strain type | Targeted Mutant Strains : Conditional mutation |
| Allele/Transgene symbol | Gt(ROSA)26Sortm14(CAG-tdTomato)Hze, Tg(Slc6a5-ERT2/Ccre)1Jhi, Tg(Gad2-Ncre/ERT2)1Jhi |
| Gene/Transgene symbol | Gt(ROSA)26Sor, Tg(Slc6a5-ERT2/Ccre)1Jhi, Tg(Gad2-Ncre/ERT2)1Jhi |
Information from provider
| Provider | Johannes Hirrlinger |
| Provider affiliation | Carl-Ludwig-Institute for Physiology, University of Leipzig |
| Additional owner | Hongkui Zheng, PhD, Allen Institute for Brain Science, Seattle, USA |
| Genetic information | This is a triple transgenic line allowing to genetically target neurons which use GABA and glycine at the same time as neurotransmitters, at a specific time point based on tamoxifen-inducible, cre recombinase-mediated DNA recombination using the split-CreERT2 system (Hirrlinger et al. 2009; doi: 10.1371/journal.pone.0008354). It contains the following three transgenic alleles: 1) BAC[Gad2-NCreERT2-IRES-beta galactosidase-SV40pA] in which the NCreERT2-IRES-beta galactosidase-SV40pA sequence was inserted by homologous recombination into BAC clone 407K8 at the ATG initiation codon of exon 1 of the Gad2 gene. 2) BAC[Slc6a5-ERT2CCre-IRES-alkaline phosphatase-SV40pA] in which the ERT2CCre-IRES- alkaline phosphatase-SV40pA sequence was inserted by homologous recombination into exon 2 of the Slc6a5 gene (also known as glycine transporter 2, GlyT2) within BAC clone 365E4 using homologous recombination. 3) The Gt(ROSA)26Sortm14(CAG-tdTomato)Hze (Ai14) reporter allele expressing tdTomato after cre-mediated DNA recombination (Madisen et al. 2010, DOI: 10.1038/nn.2467). |
| Phenotypic information | Homozygous:The mice do not show any general phenotype. However, neurons which at the same time of tamoxifen injection use both GABA and glycine as neurotransmitter (i.e. GABA/glycine co-transmitting neurons) are labelled irreversibly due to tdTomato expression from the Ai14 reporter allele induced by cre recombinase/loxP-mediated DNA recombination. Besides its use to track co-transmitting neurons by labelling via reporter allele expression, this mouse line can be combined with any mouse line harboring a loxP-flanked gene to delete it in co-transmitting neurons. Furthermore, each single allele (Gad2-NCreERT2 as well as Slc6a5-ERT2CCre) can be used on its own (after appropriate crossings to remove the other allele) to be combined with any other split-CreERT2 based transgene to change the cell type specificity of recombination.Heterozygous:Same as homozygous |
| Breeding history | Transgenic strains BAC[Gad2-NCreERT2-IRES-beta galactosidase-SV40pA] and BAC[Slc6a5-ERT2CCre-IRES-alkaline phosphatase-SV40pA] were generated individually by oocyte injections of the BAC constructs. Lines were then crossed with each other as well as with the Ai14 reporter line. In most animals, the Ai14 reporter allele is maintained homozygous, while the two BAC-based split-cre recombinase alleles are heterozygous. The BAC constructs were initially injected into C57BL/6N oocytes. In the further course, however, they were paired with C57BL/6J. The reporter mouse line Ai14 was obtained from another lab in a C57BL/6 background (not specified if B6J or B6N). |
| References |
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| Homozygous fertile | yes |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Institute of Molecular Genetics, Prague, Czech Republic |
| Animals used for archiving | homozygous 0, homozygous 0 |
| Stage of embryos | 2-cell |
Disease and phenotype information
MGI phenotypes (gene matching)
- abnormal ear pigmentation / MGI
- decreased circulating LDL cholesterol level / MGI
- decreased hematocrit / MGI
- increased leukocyte cell number / MGI
- decreased neutrophil cell number / MGI
- extramedullary hematopoiesis / MGI
- abnormal erythropoiesis / MGI
- abnormal myocardial fiber morphology / MGI
- abnormal cell death / MGI
- increased granulocyte number / MGI
- increased cell proliferation / MGI
- alopecia / MGI
- short snout / MGI
- abnormal digestive system morphology / MGI
- gastrointestinal hemorrhage / MGI
- increased rib number / MGI
- abnormal pulmonary artery morphology / MGI
- rectal prolapse / MGI
- abnormal renal/urinary system morphology / MGI
- abnormal mammary gland development / MGI
- abnormal spleen morphology / MGI
- enlarged spleen / MGI
- enlarged lymph nodes / MGI
- dystrophic muscle / MGI
- absent notochord / MGI
- abnormal retinal photoreceptor morphology / MGI
- abnormal neuromuscular synapse morphology / MGI
- pigmentation phenotype / MGI
- increased body weight / MGI
- decreased body weight / MGI
- decreased body size / MGI
- retinal degeneration / MGI
- disorganized retinal layers / MGI
- abnormal optic nerve morphology / MGI
- decreased anxiety-related response / MGI
- circling / MGI
- hypoactivity / MGI
- impaired coordination / MGI
- abnormal eating behavior / MGI
- limb grasping / MGI
- increased circulating triglyceride level / MGI
- increased circulating free fatty acid level / MGI
- increased circulating HDL cholesterol level / MGI
- hyperglycemia / MGI
- anemia / MGI
- abnormal blood vessel morphology / MGI
- abnormal mesoderm development / MGI
- abnormal somite development / MGI
- decreased trophoblast giant cell number / MGI
- postnatal growth retardation / MGI
- impaired wound healing / MGI
- abnormal humoral immune response / MGI
- arrested B cell differentiation / MGI
- arrested T cell differentiation / MGI
- increased inflammatory response / MGI
- reduced fertility / MGI
- reduced female fertility / MGI
- male infertility / MGI
- decreased litter size / MGI
- respiratory distress / MGI
- abnormal pain threshold / MGI
- increased thermal nociceptive threshold / MGI
- abnormal coat/hair pigmentation / MGI
- abnormal glucose homeostasis / MGI
- increased circulating insulin level / MGI
- premature death / MGI
- abnormal tail morphology / MGI
- abnormal kidney morphology / MGI
- abnormal neural tube morphology / MGI
- no abnormal phenotype detected / MGI
- abnormal seminiferous tubule morphology / MGI
- small lymph nodes / MGI
- abnormal spleen white pulp morphology / MGI
- abnormal bone marrow cell morphology/development / MGI
- abnormal megakaryocyte progenitor cell morphology / MGI
- abnormal proerythroblast morphology / MGI
- abnormal megakaryocyte morphology / MGI
- increased mean corpuscular volume / MGI
- decreased mean corpuscular volume / MGI
- increased mean platelet volume / MGI
- hepatic steatosis / MGI
- abnormal epididymis morphology / MGI
- vestigial tail / MGI
- reticulocytosis / MGI
- abnormal keratinocyte differentiation / MGI
- decreased circulating corticosterone level / MGI
- asthenozoospermia / MGI
- oligozoospermia / MGI
- abnormal renal tubule morphology / MGI
- decreased circulating insulin level / MGI
- abnormal chemical nociception / MGI
- dilated heart left ventricle / MGI
- decreased vertical activity / MGI
- abnormal notochord morphology / MGI
- abnormal ocular fundus morphology / MGI
- albuminuria / MGI
- decreased hemoglobin content / MGI
- decreased erythrocyte cell number / MGI
- no phenotypic analysis / MGI
- vertebral transformation / MGI
- abnormal lumbar vertebrae morphology / MGI
- abnormal skeletal muscle fiber morphology / MGI
- absent allantois / MGI
- hypospadia / MGI
- anal atresia / MGI
- increased erythroid progenitor cell number / MGI
- abnormal embryonic hematopoiesis / MGI
- kinked neural tube / MGI
- epididymal inflammation / MGI
- nervous system phenotype / MGI
- abnormal nervous system morphology / MGI
- kidney cysts / MGI
- pallor / MGI
- abnormal neural tube closure / MGI
- abnormal retinal inner nuclear layer morphology / MGI
- vascular smooth muscle hypoplasia / MGI
- skeletal muscle necrosis / MGI
- abnormal defecation / MGI
- abnormal heart left ventricle morphology / MGI
- abnormal circulating lipid level / MGI
- abnormal hormone level / MGI
- increased lean body mass / MGI
- abnormal rod electrophysiology / MGI
- abnormal cone electrophysiology / MGI
- caudal body truncation / MGI
- abnormal vitelline vascular remodeling / MGI
- abnormal sarcomere morphology / MGI
- increased compact bone thickness / MGI
- transmission ratio distortion / MGI
- abnormal basement membrane morphology / MGI
- short frontal bone / MGI
- short nasal bone / MGI
- increased incidence of tumors by chemical induction / MGI
- caudal vertebral transformation / MGI
- cervical vertebral transformation / MGI
- lumbar vertebral transformation / MGI
- thoracic vertebral transformation / MGI
- cervical vertebral fusion / MGI
- absent caudal vertebrae / MGI
- small sacral vertebrae / MGI
- abnormal vertebral column morphology / MGI
- notochord degeneration / MGI
- truncated notochord / MGI
- abnormal platelet morphology / MGI
- decreased susceptibility to experimental autoimmune encephalomyelitis / MGI
- increased hematopoietic stem cell number / MGI
- decreased testis weight / MGI
- increased energy expenditure / MGI
- decreased adiponectin level / MGI
- decreased epididymis weight / MGI
- abnormal epididymis epithelium morphology / MGI
- skin inflammation / MGI
- decreased B-1 B cell number / MGI
- increased neuronal precursor cell number / MGI
- increased osteoblast cell number / MGI
- decreased lymphocyte cell number / MGI
- decreased cardiac muscle contractility / MGI
- cachexia / MGI
- increased susceptibility to injury / MGI
- decreased circulating cholesterol level / MGI
- abnormal retinal pigment epithelium morphology / MGI
- abnormal rostral-caudal axis patterning / MGI
- glomerulosclerosis / MGI
- increased oxygen consumption / MGI
- impaired glucose tolerance / MGI
- spina bifida occulta / MGI
- decreased triglyceride level / MGI
- abnormal renal glomerulus morphology / MGI
- insulin resistance / MGI
- muscle phenotype / MGI
- homeostasis/metabolism phenotype / MGI
- growth/size/body region phenotype / MGI
- endocrine/exocrine gland phenotype / MGI
- cardiovascular system phenotype / MGI
- immune system phenotype / MGI
- reproductive system phenotype / MGI
- skeleton phenotype / MGI
- hematopoietic system phenotype / MGI
- increased circulating thyroxine level / MGI
- increased circulating triiodothyronine level / MGI
- abnormal skeleton morphology / MGI
- abnormal body temperature / MGI
- choroidal neovascularization / MGI
- abnormal eye electrophysiology / MGI
- decreased circulating glucose level / MGI
- increased mean corpuscular hemoglobin / MGI
- decreased mean corpuscular hemoglobin / MGI
- decreased angiogenesis / MGI
- increased bone mass / MGI
- abnormal cell physiology / MGI
- increased susceptibility to diet-induced obesity / MGI
- decreased susceptibility to diet-induced obesity / MGI
- decreased circulating leptin level / MGI
- increased circulating leptin level / MGI
- increased mitochondrial fission / MGI
- increased apoptosis / MGI
- abnormal tail development / MGI
- abnormal spermatid morphology / MGI
- intestine polyps / MGI
- abnormal paraxial mesoderm morphology / MGI
- abnormal podocyte slit diaphragm morphology / MGI
- decreased CD4-positive, alpha beta T cell number / MGI
- decreased CD8-positive, alpha-beta T cell number / MGI
- abnormal granulocyte differentiation / MGI
- abnormal monocyte differentiation / MGI
- podocyte foot process effacement / MGI
- increased germinal center B cell number / MGI
- decreased B-2 B cell number / MGI
- decreased mature B cell number / MGI
- increased megakaryocyte cell number / MGI
- abnormal bone ossification / MGI
- retinal photoreceptor degeneration / MGI
- abnormal medium spiny neuron morphology / MGI
- retinal outer nuclear layer degeneration / MGI
- increased circulating tumor necrosis factor level / MGI
- increased circulating interleukin-1 alpha level / MGI
- increased circulating interleukin-1 beta level / MGI
- increased interleukin-17 secretion / MGI
- decreased survivor rate / MGI
- increased B cell apoptosis / MGI
- increased liver iron level / MGI
- increased spleen iron level / MGI
- increased circulating iron level / MGI
- lipofuscinosis / MGI
- abnormal physiological response to xenobiotic / MGI
- decreased erythroid progenitor cell number / MGI
- anal stenosis / MGI
- hairpin sperm flagellum / MGI
- increased abdominal fat pad weight / MGI
- increased trophoblast giant cell number / MGI
- centrally nucleated skeletal muscle fibers / MGI
- skeletal muscle endomysial fibrosis / MGI
- abnormal synaptonemal complex / MGI
- abnormal mammary gland duct morphology / MGI
- decreased thymocyte apoptosis / MGI
- enlarged popliteal lymph nodes / MGI
- decreased birth body size / MGI
- impaired somite development / MGI
- increased total body fat amount / MGI
- abnormal placenta physiology / MGI
- abnormal retinal blood vessel morphology / MGI
- decreased mammary gland epithelial cell proliferation / MGI
- decreased tumor latency / MGI
- altered tumor pathology / MGI
- mortality/aging / MGI
- integument phenotype / MGI
- increased bone volume / MGI
- abnormal double-strand DNA break repair / MGI
- neonatal lethality, complete penetrance / MGI
- perinatal lethality, incomplete penetrance / MGI
- prenatal lethality, complete penetrance / MGI
- embryonic lethality during organogenesis, complete penetrance / MGI
- preweaning lethality, complete penetrance / MGI
- prenatal lethality, incomplete penetrance / MGI
- embryonic lethality during organogenesis, incomplete penetrance / MGI
- abnormal anterior visceral endoderm cell migration / MGI
- increased circulating erythropoietin level / MGI
- renal tubule atrophy / MGI
- lethality, complete penetrance / MGI
- increased mitochondria number / MGI
- rectal atresia / MGI
- rectourethral fistula / MGI
- increased hematopoietic stem cell proliferation / MGI
- increased food intake / MGI
- impaired mammary gland growth during pregnancy / MGI
- decreased paraxial mesoderm size / MGI
- abnormal skeletal muscle regeneration / MGI
- testis degeneration / MGI
- preputial gland inflammation / MGI
- nervous system inclusion bodies / MGI
- decreased fatty acid beta-oxidation / MGI
- epididymis hypertrophy / MGI
- spermatocele / MGI
- epididymis fibrosis / MGI
- increased epididymal cell proliferation / MGI
- increased epididymal epithelium cell proliferation / MGI
- increased heart iron level / MGI
- increased intestinal iron level / MGI
Literature references
- GABA-Glycine Cotransmitting Neurons in the Ventrolateral Medulla: Development and Functional Relevance for Breathing.;Hirrlinger Johannes, Marx Grit, Besser Stefanie, Sicker Marit, Köhler Susanne, Hirrlinger Petra G, Wojcik Sonja M, Eulenburg Volker, Winkler Ulrike, Hülsmann Swen, ;2019;Frontiers in cellular neuroscience;13;517; 31803026