C57BL/6-Flt3l^tm1Imx/TacMmjax

Stock number: 025411
Product name: Flt3-L^-
Research areas: Immunology, Inflammation and Autoimmunity Research

Description

These Flt3l (FMS-like tyrosine kinase 3 ligand) KO mice exhibit reduced numbers of leukocytes in bone marrow, peripheral blood, lymph nodes and spleen and decreased number of dendritic cells in the spleen, thymus, and lymph nodes. This strain may be useful for studying expansion of early hematopoietic progenitor cells and dendritic cell homeostasis.

Detailed description

Flt3l (FMS-like tyrosine kinase 3 ligand) encodes a nonredundant, critical cytokine involved in dendritic cell homeostasis. Its ligand Flt3 is a class III receptor tyrosine kinase expressed on hematopoietic progenitor cells with dendritic cell development potential. Mice homozygous for this null allele exhibit reductions in lymphohematopoietic progentors and B-cell precursors. Leukocyte cellularity is reduced in the bone marrow, peripheral blood, lymph nodes and spleen. Thymic cellularity, blood hematocrit and platelet numbers are not affected. Both myeloid-related and lymphoid-related dendritic cell numbers are reduced in the spleen, lymph node and thymus. In addition, natural killer cells are markedly reduced in the spleen. This strain may be useful for studying expansion of early hematopoietic progenitor cells and dendritic cell homeostasis.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 1-5. The vector deletes the majority of the extracellular domain. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into BALB/c blastocysts. The resulting chimeric animals were crossed to C57BL/6 and offspring were intercrossed to establish a homozygous colony). In 2000, a colony was established at the Emerging Models NIAID repository at Taconic. In 2014 the line was transferred to the MMRRC at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

 

Allele

Symbol: Flt3l^tm1Imx
Name: targeted mutation 1, Immunex Corporation
MGI accession ID: MGI:2158499
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Flt3l
Marker name: FMS-like tyrosine kinase 3 ligand
Chromosome: 7
Strain of origin: C57BL/6
Molecular note: A neomycin selection cassette replaced a genomic fragment containing the initiation codon and most of the sequences encoding the extracellular domain. RT-PCR analysis on RNA derived from spleen and bone marrow of homozygous mice confirmed that no detectable transcript is produced from this allele.
General note: The ES cell line was described as C57BL/6 derived.