Homozygous Lyve1tm1Lhua knock-out mice exhibit abnormal lymphatic capillary vessel morphology in the liver and intestines with increased intradermal interstitial-lymphatic flow.
Jung S. Huang, St. Louis University School of Medicine
Homozygotes are viable and fertile, and produce normal-sized litter. No gross phenotypic or behavioral abnormalities have been reported, even in older (2 year old) mice. Homozygous mutants express neither endogenous RNA or protein in liver tissue. Lymphatic capillary vessel morphology in the liver and intestines of homozygous mice is abnormal, with vessels having distended or rounded lumens in contrast to the smaller, typically collapsed, irregular shapes observed in wildtype controls. Intradermal interstitial-lymphatic flow also is increased. Syngenic tumor cell transplants into grow more rapidly and robustly in homozygous mutant mice compared with transplants into wildtype mice, and develop porous interstitial spaces. These mutant mice may be useful in studies of structural and functional characteristics of the lymphatic system, cell-surface retention sequence (CRS) motif-containing growth factor secretion, autocrine and paracrine regulation of cell growth, as well as of cancer and the mechanisms of metastasis.
A targeting vector was designed to replace a portion of exon 2 and all of exon 3 of the endogenous gene with a male-germline, self-excising loxP-flanked cassette (itself containing a neomycin resistance (Neo) gene and a testes-specific angiotensin-converting enzyme (tACE) promoter-driven Cre recombinase gene). The construct was electroporated into 129S1/Sv-derived W9.5 embryonic stem (ES) cells. Correctly targeted ES clones were injected into C57BL/6J blastocysts and chimeric males were backcrossed for germ-line transmission to C57BL/6J females. The resulting cassette-excised offspring (containing a single loxP site in place of the 3' region of exon 2 and all of exon 3) were backcrossed for 6 generations onto the C57BL/6 genetic background prior to arrival at The Jackson Laboratory.
|Allele Name||targeted mutation 1, Jung S Huang|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Lyve1, lymphatic vessel endothelial hyaluronan receptor 1|
|Strain of Origin||129S1|
|Molecular Note||A targeting vector was designed to remove parts of exon 2, intron 2, exon 3 and intron 3 of the gene, and also to create a frame shift. The vector contained a floxed cassette containing a neomycin resistance gene and a testes specific angiotensin-converting enzyme promoter driving expression of cre recombinase. The floxed cassette was excised from the locus upon passage through the male germline.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the CRSBP-1 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #006221 in your Materials and Methods section.