B6.129S-Flt3^tm1Irl/MbogJ

Stock number: 036467
Product name: flk2-
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research

Description

flk2 knockout mice have a neomycin cassette inserted into exon 3 of the FMS-like tyrosine kinase 3 (Flt3) gene. Homozygous mice exhibit fewer numbers of pro-B and pre-B cells in bone marrow as well as decreased numbers of dendritic cells. This strain may be useful for studies of multipotent stem cells and lymphoid differentiation.

Detailed description

Flt3 (FMS-like tyrosine kinase 3 or Flk2) encodes a receptor tyrosine kinase involved in the regulation of hematopoiesis. Mutations in Flt3 are associated with some leukemias. flk2 knockout mice have a neomycin cassette inserted into exon 3 that results in a frameshift that creates a stop codon. Mice homozygous for the mutation are viable and fertile with a mostly normal hematopoietic system. Bone marrow from flk2^-/- mice contains significantly fewer numbers of pro-B cells (49% of control) and somewhat reduced numbers of pre-B cells (74% of control), however, numbers of differentiated B cells are normal. Myeloid cell lineages are not affected. In addition, loss of Flt3 results in fewer numbers of plasmacytoid dendritic cells and conventional dendritic cells. This strain may be useful for studies of multipotent stem cells and lymphoid differentiation.

Development

The flk2 null allele was developed in the laboratory of Dr. Ihor Lemischka, Princeton University. The targeting vector was designed to insert a neomycin cassette into exon 3 at a position corresponding to amino acid 59 of the mature protein of the FMS-like tyrosine kinase 3 (Flt3) gene on chromosome 5. The mutation results in a frameshift that creates a stop codon after 51 amino acids. The construct was electroporated into 129S/SvEv -derived CCE embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred with C57BL/6J females and subsequently these mice were bred to C57BL/6J mice for at least 5 generations. Dr. Milena Bogunovic (University of Massachusetts) obtained flk2 null mice from Dr. Lemischka and maintained the allele as a homozygous colony. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Flt3^tm1Irl
Name: targeted mutation 1, Ihor R Lemischka
MGI accession ID: MGI:2384051
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Flk2^-
Marker symbol: Flt3
Marker name: FMS-like tyrosine kinase 3
Marker synonyms: CD135; FLK2; FLK-2; Flt-3; STK1; wmfl
Chromosome: 5
Strain of origin: 129S/SvEv-Gpi1^c
Molecular note: Exon 3 was disrupted by the insertion of a neomycin selection cassette at the codon corresponding to residue 59 in the mature protein. An RNAse protection assay detected low levels of transcript in homozygous mutant mice. RT-PCR and sequence analyses of the mutant transcript showed that the targeted exon 3 had been excised, resulting in a frameshift mutation that introduces a stop codon after codon 51.