B6.129S1-Lyve1^tm1Lhua/J

Stock number: 006221
Product name: CRSBP-1 KO
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Homozygous Lyve1^tm1Lhua knock-out mice exhibit abnormal lymphatic capillary vessel morphology in the liver and intestines with increased intradermal interstitial-lymphatic flow.

Detailed description

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.

Development

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

Symbol: Lyve1^tm1Lhua
Name: targeted mutation 1, Jung S Huang
MGI accession ID: MGI:3697727
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Lyve1
Marker name: lymphatic vessel endothelial hyaluronan receptor 1
Chromosome: 7
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.