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LoxP sites have been inserted into the introns around exon 4 of the versican (Vcan) gene. The neomycin cassette has been removed.
Conditional phenotype: Th versican-floxed strain does have a conditional phenotype when bred to a mouse strain expressing Cre-recombinase and when treated with some type of stressor. Several publications describe the conditional phenotype using various Cre-recombinase mice and mouse models (see reference list below).
The targeted mutation of the versican gene was accomplished using a vector that was linearized and used for electroporation of C57BL/6NHsd-derived embryonic stem cells (C57BL/6-EZ Mouse ESCs; Catalog #: ASE-9007, Applied Stem Cell), which was performed by the University of Washington Transgenic Resources Program. The ESC clones were screened by PCR, and recombination was identified by Southern blot analysis. ESCs were injected into C57BL/6N mouse blastocysts, and chimeras were obtained. Germline transmission of intact mutation was confirmed by Southern blot analysis. To remove the neomycin selection cassette the Vcantm1.1Cwf mouse strain was bred to the B6.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/RainJ mouse strain (RRID:IMSR_JAX:009086). The Vcantm1.1Cwf mouse strain was backcrossed to C57BL/6J mice at least 5 times. This included 3 backcrosses using the genome scanning services at The Jackson Laboratories. Additionally, the Vcantm1.1Cwf mouse strain was backcrossed to C57BL/6J males to ensure the Y chromosome was from the C57BL/6J strain.
Chang MY, Kang I, Gale M Jr, Manicone AM, Kinsella MG, Braun KR, Wigmosta T, Parks WC, Altemeier WA, Wight TN, Frevert CW. Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs. Am J Physiol Lung Cell Mol Physiol. 2017 Dec 1;313(6):L1069-L1086. doi: 10.1152/ajplung.00353.2017. Epub 2017 Sep 14. (Medline PMCID: 5814701)
Kang I, Harten IA, Chang MY, Braun KR, Sheih A, Nivison MP, Johnson PY, Workman G, Kaber G, Evanko SP, Chan CK, Merrilees MJ, Ziegler SF, Kinsella MG, Frevert CW, Wight TN. Versican Deficiency Significantly Reduces Lung Inflammatory Response Induced by Polyinosine-Polycytidylic Acid Stimulation. J Biol Chem. 2017 Jan 6;292(1):51-63. doi: 10.1074/jbc.M116.753186. Epub 2016 Nov 28. (Medline PMCID: 5217699)
Kellar GG, Barrow KA, Rich LM, Debley JS, Wight TN, Ziegler SF, Reeves SR. Loss of versican and production of hyaluronan in lung epithelial cells are associated with airway inflammation during RSV infection. J Biol Chem. 2021 Jan-Jun;296:100076. doi: 10.1074/jbc.RA120.016196. Epub 2020 Nov 21. (Medline PMID: 33187989)
Chang MY, Kang I, Gale M Jr, Manicone AM, Kinsella MG, Braun KR, Wigmosta T, Parks WC, Altemeier WA, Wight TN, Frevert CW. Versican is produced by Trif- and type I interferon-dependent signaling in macrophages and contributes to fine control of innate immunity in lungs. Am J Physiol Lung Cell Mol Physiol. 2017 Dec 1;313(6):L1069-L1086. doi: 10.1152/ajplung.00353.2017. Epub 2017 Sep 14. (Medline PMID: 28912382)
Kang I, Harten IA, Chang MY, Braun KR, Sheih A, Nivison MP, Johnson PY, Workman G, Kaber G, Evanko SP, Chan CK, Merrilees MJ, Ziegler SF, Kinsella MG, Frevert CW, Wight TN. Versican Deficiency Significantly Reduces Lung Inflammatory Response Induced by Polyinosine-Polycytidylic Acid Stimulation. J Biol Chem. 2017 Jan 6;292(1):51-63. doi: 10.1074/jbc.M116.753186. Epub 2016 Nov 28. (Medline PMID: 27895126)
Han CY, Kang I, Harten IA, Gebe JA, Chan CK, Omer M, Alonge KM, den Hartigh LJ, Gomes Kjerulf D, Goodspeed L, Subramanian S, Wang S, Kim F, Birk DE, Wight TN, Chait A. Adipocyte-Derived Versican and Macrophage-Derived Biglycan Control Adipose Tissue Inflammation in Obesity. Cell Rep. 2020 Jun 30;31(13):107818. doi: 10.1016/j.celrep.2020.107818. (Medline PMID: 32610121)
Colony Surveillance Program and Current Health Reports
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Cryopreserved material may be available upon request, please inquire to mmrrc@ucdavis.edu for more information.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
The donor or their institution limits the distribution to non-profit institutions only.
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.