STOCK Bcl11a^tm1.2Leid/J

Stock number: 038391
Product name: Ctip1^fl , Bcl11a^L2
Research areas: Dermatology Research, Internal/Organ Research, Metabolism Research, Research Tools

Description

Bcl11a^L2 (or Ctip^fl) mice possess loxP sites flanking exons 3-4 of the Bcl11a (B cell CLL/lymphoma 11A [zinc finger protein], also known as Ctip1) gene. These floxed mice are useful for tissue specific deletion of Bcl11a when studying skin disorders.

Detailed description

Bcl11a (B cell CLL/lymphoma 11A [zinc finger protein], also known as Ctip1) encodes a zinc finger transcriptional factor involved in lymphopoiesis, epithelial development, adult epidermal homeostasis, and as a negative regulator of wound healing. BCL11A is highly expressed in developing murine skin. Germline deletion of Bcl11a results in perinatal lethality, defects in the epidermal permeability barrier (EPB) of embryonic skin and epidermal differentiation, reduced numbers of lamellar bodies in granular layers, and altered lipid composition of the skin epidermis.

Bcl11a^L2 (or Ctip^fl) mice possess loxP sites flanking exon 3 and 4 of the Bcl11a gene. Exons 3 and 4 encode 75% of the protein coding sequence as well as the DNA binding domain. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-4 deleted in the cre-expressing tissues resulting in a tissue specific null allele.

When combined with mice carrying a Cre recombinase that is expressed in skin (such as Tg(KRT14-cre)1Amc, Stock No. 004782), progeny exhibit increased keratinocyte proliferation/differentiation, and accelerated cutaneous wound healing.

Development

The Bcl11a^L2 (or Ctip^fl) targeting vector initally was designed to insert loxP sites flanking exon 4 and an FRT-flanked neomycin cassette in reverse orientation downstream of exon 4 in the B cell CLL/lymphoma 11A [zinc finger protein] (Bcl11a also known as Ctip1) locus on chromosome 11. In this targeting event the upstream loxP site was lost. A second targeting event used the 129S2/SvPas-derived embryonic stem cells from the first targeting event and placed a LoxP-Hygro-LoxP upstream of exon 3, and generated mice with LoxP-Hygro-LoxP-Exon 3-Exon 4-LoxP. Exons 3 and 4 encode 75% of the protein coding sequence as well as the DNA binding domain. Chimeric males were crossed to C57BL/6 females. The neo was subsequently removed by breeding using a mouse of unknown background carrying the Tg(ACTFLPe)9205Dym allele. The hygro cassette was removed by breeding using a mouse of unknown background carrying the Tg(CMV-cre)1Ipc allele. The strain has been backcrossed to C57BL/6 for more than 5 generations by the donating investigator (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).



In 2023, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Many of the markers throughout the genome were segregating with 129 and many were segregating with an unknown source. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Bcl11a^tm1.2Leid
Name: targeted mutation 1.2, Mark Leid
MGI accession ID: MGI:7506863
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Bcl11a^L2; Bcl11a^tm1.2Akin
Marker symbol: Bcl11a
Marker name: B cell CLL/lymphoma 11A (zinc finger protein)
Marker synonyms: 2810047E18Rik; COUP-TF interacting protein 1; CTIP1; D930021L15Rik; DILOS; Evi9; Evi9a; Evi9b; Evi9c; HBFQTL5; mKIAA1809; mouse myeloid leukemia gene; SMARCM1; ZNF856
Chromosome: 11
Strain of origin: 129S2/SvPas
Molecular note: The first targeting vector is designed to insert loxP sites flanking exon 4 and an FRT-flanked neomycin cassette in reverse orientation downstream of exon 4. In this targeting event the upstream loxP site was lost. A second targeting event used the 129S2/SvPas-derived embryonic stem cells from the first targeting event and placed a LoxP-Hygro-LoxP upstream of exon 3, and generated mice with LoxP-Hygro-LoxP-Exon3 -Exon 4-LoxP. Flp-mediated recombination removed the neo cassette. Cre-mediated recombination removed the hygro cassette. Exons 3 and 4 encode 75% of the protein coding sequence as well as the DNA binding domain.