FVB/N-Tg(tetO-BCR/ABL1)2Dgt/J

Stock number: 006202
Product name: BCR-ABL1
Research areas: Cancer Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Under the control of a tetracycline-responsive promoter element (tetO), expression of the BCR-ABL1 fusion protein can be regulated in the appropriate tissue of bitransgenic offspring by tissue-specific promoters driving a transactivator protein (rtTA or tTA).

Detailed description

Hemizygotes are viable, fertile, normal in size, and do not display any behavioral abnormalities. Transgene expression is directed by the tetracycline-responsive element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing either reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters , BCR-ABL1 fusion protein expression can be regulated in the appropriate tissue of the bitransgenic offspring with the tetracycline analog, doxycycline.

These mice originally were designed to be bred with transgenic mice harboring a Tal1-tTA transgene (see Stock No. 006209), creating double transgenic offspring as a model for studies of the Philadelphia chromosome and inducible chronic myeloid leukemia.

When bred to a strain expressing tTA in the epithelial cells of secretory organs and skin (see Stock No. 002618 - Tg(MMTVtTa)1Mam), this mutant mouse strain may be useful in studies of leukemia.

When bred to a strain expressing tTA in thebone marrow hematopoietic stem cells and in common myeloid progenitors (see Stock No. 017722 - Tg(Tal1-tTA)19Dgt), this mutant mouse strain may be useful in studies of chronic myeloid leukemia.

Development

A transgene was generated containing a human p210 BCR-ABL1 fusion protein cDNA sequence under transcriptional control of the tetracycline-responsive element (TRE; tetO) sequence fused to a minimal cytomegalovirus (hCMV) promoter. The transgene was injected into fertilized FVB/N eggs. Transgenic offspring (founder line 2) were maintained by breeding transgenic mice to either FVB/N inbred mice or wildtype siblings for many generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Tg(tetO-BCR/ABL1)2Dgt
Name: transgene insertion 2, Daniel G Tenen
MGI accession ID: MGI:2387680
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(tetO-BCR/ABL1)2Dgt
Marker name: transgene insertion 2, Daniel G Tenen
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: BCR,BCR, RhoGEF and GTPase activating protein,human; ABL1,ABL proto-oncogene 1, non-receptor tyrosine kinase,human
Molecular note: The transgene contains a cDNA encoding the human p210 BCR-ABL1 fusion protein (B3A2 form; J:86227) under transcriptional control of the tetracycline-responsive element (tetO; also called TRE) fused to a minimal cytomegalovirus (CMV) promoter. In doubly transgenic mice expressing a tetracycline transactivator or reverse transactivator protein under the control of a ubiquitous or tissue-specific promoter, expression of the BCL-ABL1 fusion gene can be controlled temporally by withdrawal or administration of a tetracycline analog.
General note: This record is also representative of lines 3 and 4 that were also generated; all of these lines exhibit a similar phenotype in combination with Tg(MMTVtTA)1Mam. Bitransgenic mice with this transgene in combination with Tg(MMTVtTA)1Mam, when tetracycline administration is stopped, are models for B cell acute lymphoblastic leukemia (ALL); line 2 exhibits the greatest leukemia susceptibility (Figure 1). (J:72377)