IMPC phenotypes (gene matching)
B6;129P2-Bcl11bem1Srft/H
| Status | Available to order |
| EMMA ID | EM:13082 |
| Citation information | RRID:IMSR_EM:13082 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;129P2-Bcl11bem1Srft/H |
| Alternative name | BCL11B p.R3S |
| Strain type | Endonuclease-mediated |
| Allele/Transgene symbol | Bcl11bem1 |
| Gene/Transgene symbol | Bcl11b |
Information from provider
| Provider | Stephen Twigg |
| Provider affiliation | The MRC Weatherall Institute of Molecular Medicine |
| Genetic information | Mouse embryonic stem (ES) cells (E14Tg2aIV, 129P2/OlaHsd) were transfected with pX458 (Addgene 48 138) containing a guide sequence targeting a region near the Bcl11b translation start site (5-CCGCAAACAGGGCAACCCGC-3) and an oligonucleotide donor for homology directed repair and introduction of the c.7C to A mutation (5-gcggcggcggcggctcagaccccctccccggcccgcatctgtg cagctttccgggcgatgccagaatagatgccgGggcaatgtccAg ccgcaaacagggcaacccgcagcacttgtcccagaggga-3). Briefly, ES cells were seeded onto gelatin-coated 6-well plates at 3×10^5 cells per well 1 day before transfection with 3.3 μg plasmid, 10 μl of 10 μM donor complexed with 20 μl Fugene HD (Promega) oligonucleotide in a total volume of 100 μl made up with serum free medium. After 24 h, cells were sorted for green fluorescent protein-positive cells using fluorescence-activated cell sorting in a 96-well format. A homozygous c.7C to A ES clone was identified and was injected into blastocysts (C57BL/6) for chimera generation. Several chimeric mice were produced, and the mutant allele was successfully transmitted through the germline. |
| Phenotypic information | Homozygous:Homozygous mouse is not viable (neonatal lethality).Heterozygous:Heterozygous, Bcl11bR3S/+mice were born at Mendelian ratios, survived into adulthood without gross anatomical abnormalities and bred normally. However, examination of calvarial sutures by micro-CT revealed that Bcl11bR3S/+ mice exhibited variable and partial, bilateral osteogenic fusion of the coronal suture that was accompanied by narrowing of the sagittal and lambdoid sutures by ca. 50% at P0. Other calvarial and facial sutures in the Bcl11bR3S/+ mice were indistinguishable from those of wild-type mice. Homozygous, mutant mice (Bcl11bR3S/R3S) recapitulated perinatal lethality of Bcl11b−/− mice, due to apparent respiratory insufficiency, as well as multi-suture craniosynostosis at P0 involving the coronal (bilateral), interfrontal, sagittal, interparietal and temporal sutures. However, in marked contrast to Bcl11b−/− mice or those lacking BCL11B in cells derived from neural crest, Bcl11bR3S/R3S mice did not exhibit fusion of facial sutures. The sutural mesenchyme of the facial skeleton is the most sensitive to loss of BCL11B and frequently undergoes premature osteogenic differentiation in Bcl11b+/− heterozygotes |
| Breeding history | Founder line: M00770521 (chimeric founder line) Original genetic background: E14Tg2aIV, 129P2/OlaHsd Current genetic background: C57BL/6 |
| References |
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| Homozygous fertile | no |
| Homozygous viable | no |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Mary Lyon Centre at MRC Harwell, Oxford, United Kingdom |
| Animals used for archiving | heterozygous C57BL/6J males |
| Breeding at archiving centre | Gene targeting was performed in E14Tg2aIV (129P2/OlaHsd) ES cells. The ES cells were injected into C57BL/6J-derived blastocysts. All subsequent crosses have been to C57BL/6J mice. |
Disease and phenotype information
Literature references
- A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis.;Goos Jacqueline A C, Vogel Walter K, Mlcochova Hana, Millard Christopher J, Esfandiari Elahe, Selman Wisam H, Calpena Eduardo, Koelling Nils, Carpenter Evan L, Swagemakers Sigrid M A, van der Spek Peter J, Filtz Theresa M, Schwabe John W R, Iwaniec Urszula T, Mathijssen Irene M J, Leid Mark, Twigg Stephen R F, ;2019;Human molecular genetics;28;2501-2513; 31067316