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.
Dr. Jacques Peschon, Amgen
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.
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 Name||targeted mutation 1, Immunex Corporation|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||FL-; FLT3L-; Flt3-L-|
|Gene Symbol and Name||Flt3l, FMS-like tyrosine kinase 3 ligand|
|Strain of Origin||C57BL/6|
|General Note||The ES cell line was described as C57BL/6 derived.|
|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.|
While maintaining a live colony, these mice are bred as homozygotes. This strain is immunodeficient and should be housed at the appropriate SPF health status.
When using the Flt3-L- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #37395 in your Materials and Methods section.