B6.Cg-Cldn12tm1(KOMP)Vlcg Cldn3tm1.1Hedv/Ph
| Status | Available to order |
| EMMA ID | EM:11253 |
| International strain name | B6.Cg-Cldn12tm1(KOMP)Vlcg Cldn3tm1.1Hedv/Ph |
| Alternative name | Cldn12xCldn3BL/6 |
| Strain type | Targeted Mutant Strains : Knock-out |
| Allele/Transgene symbol | Cldn12tm1(KOMP)Vlcg, |
| Gene/Transgene symbol | Cldn12 |
Information from provider
| Provider | Rosel Blasig |
| Provider affiliation | Molecular Cellphysiology, Leibniz Institute of Molecular Pharmacology |
| Genetic information | Cldn12 region (1 exon) in chromosome 5; ES cell clones from KOMP Repository (http://www.velocigene.com/komp/detail/13208); cassettes with lacZ reporter gene and floxed neomycin gene replaced the Cldn12 exon. ES cell clones were injected into albinotic donor embryos with C57BL/6 background resulting in chimeric mice. Male chimeras with germline transmission after breeding with C57BL/6 females were used to produce offsprings, which were mated with Cldn3 knock-out C57BL/6 females (2 lines). Opposite matings with female Cldn12 and male Cldn3 C57BL/6 mice were also done (2 lines) and offsprings of all 4 lines were used for mating and backcrossing. The aim was to observe the impact of deletion of two tight junction proteins, Cldn12 as well as Cldn3 (on C57BL/6 background). |
| Phenotypic information | Homozygous:The Cldn12 x Cldn3 double-deficient mice reach normal age and size, and are fertile. The mutated mice show good general health and normal activity. The main physiological functions appear unaffected. No macroscopic lesions were noticed. The phenotype of Cldn12 single-deficient mice is among others denoted by extenuated neurotransmission and slight inflammatory alterations. Cldn3 single-deficiency reveals opening of cerebral tissue barriers, which is accompanied by infiltration of leukocytes and inflammatory lesions in the brain. The mice show enhanced susceptibility against neurodegenerative disorders such as related to multiple sclerosis. As both Cldn12 and Cldn3 are tight junction molecules, the double knock-out strain has been generated to clarify the contribution of endothelial and epithelial cell barriers in the brain to neuro-inflammatory disturbances.Heterozygous:Heterozygous mice were not analysed in detail, but reach also normal age and size, and are fertile. Short description of the listed reference (PubMed ID:24356983): Results of investigations with experimental autoimmune encephalomyelitis (EAE) in Cldn3 B6 single knock-out mice combined with analyses of patients suffering from multiple sclerosis (MS). First insights were provided into the involvement of choroid plexus in multiple sclerosis and in particular the role of the CLAUDIN 3 tight junction protein was addressed in this process. |
| Breeding history | Chimeras were backcrossed once with C57BL/6N to select those males with germ line transmission followed by crossing with C57BL/6.C-Tg(CMV-cre)1Cng/J females from Jackson Laboratory. Afterwards 8 times backcrossing to C57BL/6, in summary F10 for C57BL/6. |
| 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 | heterozygous C57BL/6 |
Literature references
- Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation.;Kooij Gijs, Kopplin Kathrin, Blasig Rosel, Stuiver Marchel, Koning Nathalie, Goverse Gera, van der Pol Susanne M A, van Het Hof Bert, Gollasch Maik, Drexhage Joost A R, Reijerkerk Arie, Meij Iwan C, Mebius Reina, Willnow Thomas E, Müller Dominik, Blasig Ingolf E, de Vries Helga E, ;2014;Acta neuropathologica;128;267-77; 24356983