B6.Cg-Tg(Vav1-Mpl)EAmol/J

Stock number: 037716
Product name: MPL SV(E)
Research areas: Cancer Research, Hematological Research, Research Tools

Description

MPL SV(E) mice express a human MPL splice variant of myeloproliferative leukemia virus oncogene (Mpl) under control of the endogenous vav 1 oncogene (Vav1) promoter. Transgenic MPL SV(E) mice carry an estimated single copy of the transgene with normal phenotype. These mice may be used as a control strain for the MPL SV(A) transgenic line (Stock No. 037715) when studying myeloproliferative neoplasms (MPNs) such as polycythemia vera (PV), chronic myeloid leukemia (CML) and acute myeloid leukemia (AML).

Detailed description

Myeloproliferative neoplasms (MPNs) are clonal disorders of the hematopoietic stem cell, these include chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF). MPNs have been associated with driver mutations in the tyrosine kinase JAK2, the thrombopoietin receptor (also known as myeloproliferative leukemia virus oncogene (MPL)) and calreticulin (CALR). A unique MPL splice variant has been consistently expressed in PV patient platelets. This MPL variant includes elimination of 7 amino acids in the N-terminal domain which impairs MPL glycosylation and expression. MPL SV(E) transgenic mice harbor this MPL splice variant driven by the endogenous vav 1 oncogene (Vav1) promoter.

MPL SV(E) hemizygous and homozygous mice are viable and fertile with no observable phenotype. The donating laboratory indicates that this line carries an estimated single copy of the transgene and that the copy number is stable across multiple generations. The donating laboratory utilizes these MPL SV(E) transgenic mice as a control strain for the higher copy MPL SV(A) mutant line (Stock No. 037715).

Development

The MPL SV(E) transgene was generated using full length MPL splice variant (SV) cDNA cloned into the HS321/45-vav vector, which contains the mouse genomic Vav1 promoter sequence. Purified linearized DNA was microinjected into the pronuclei of fertilized B6SJLF1 (Stock No. 100012) oocytes. Founder line E was established and backcrossed to C57BL/6J (Stock No. 000664) for >10 generations and then maintained by crossing hemizygous mice to wildtype littermates. The donating laboratory indicates that they refreshed this transgenic line every 10 generations by breeding MPL SV(E) hemizygous mice to C57BL/6J. The donating investigator notes that this line carries an estimated single copy of the transgene and that the copy number is stable across multiple generations; however the transgene insertion site has not been confirmed. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Tg(Vav1-Mpl)EAmol
Name: transgene insertion E, Alison Moliterno
MGI accession ID: MGI:7387062
Generation method: Transgenic
Attributes: Inserted expressed sequence
Synonyms: MPLSV(E)
Marker symbol: Tg(Vav1-Mpl)EAmol
Marker name: transgene insertion E, Alison Moliterno
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Molecular note: The transgene is generated using full length Mpl splice variant (SV) cDNA cloned into the HS321/45-vav vector, which contains the mouse genomic Vav1 promoter sequence. The Mpl splice variant has 7 amino acids deleted from the N-terminal domain. Founder line E carries an estimated single copy of the transgene and that the copy number is stable across multiple generations; however the transgene insertion site has not been confirmed.