Strain Name:

B6.129P2-Lcn2tm1Aade/AkiJ

Stock Number:

024630

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Availability:

Under Development - Now Accepting Orders

Estimated Available for Distribution Date: 01-SEP-14
Use Restrictions Apply, see Terms of Use
Lcn2 deficient mice may be useful for studying the role of iron trafficking in the regulation of innate immunity.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   04-JUN-14
Specieslaboratory mouse
GenerationN10+pN1 (21-JUL-14)
Generation Definitions
 
Donating Investigator Shizuo Akira,   Osaka University

Description
A neo cassette replaces exons 2-5 of the lipocalin 2 (Lcn2) gene, abolishing gene expression. LCN2 is an iron-trafficking protein involved in apoptosis and the regulation of the innate immune systems response to bacterial growth and infection. Toll-like receptors on innate immune cells stimulate the production and secretion of LCN2 upon bacterial infection. LCN2 limits bacterial growth by iron sequestration, which is required by bacteria in order to replicate. Homozygous LCN2-deficient mice are viable and fertile and should be housed in a specific pathogen free (SPF) facility. Escherichia coli challenge causes an increase in bacterial burden in the liver and spleen along with physical signs of sepsis such as lethargy, hunched posture, and ruffled fur. E Coli infection caused no difference in leukocyte numbers, neutrophil infiltration, or tissue iron distribution. Also, after induction of accelerated nephrotoxic serum nephritis (NTS), LCN2 KO mice exhibit more glomerular damage with increased proteinuria and interstitial leukocyte accumulation than wildtype mice.

Development
A targeting vector was designed to replace exons 2-5 of the lipocalin 2 (Lcn2) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to C57BL/6J females. These mice were backcrossed for at least 10 generations to C57BL/6J mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Lcn2tm1Aade/Lcn2tm1Aade

        involves: 129P2/OlaHsd * C57BL/6
  • mortality/aging
  • increased sensitivity to induced morbidity/mortality
    • within 42 hours after E.coli H9049 infection, more than 80% of homozygotes died compared to 0% of wild-type   (MGI Ref ID J:95107)
  • immune system phenotype
  • increased susceptibility to bacterial infection
    • increased susceptibility to infection with bacteria that acquire iron through enterochelin-type siderophores (such as E.coli) but not with those that do not (such as S. aureus)   (MGI Ref ID J:95107)
  • sepsis
    • increased bacteraemia and bacterial burden in the liver and spleen after intraperitoneal challenge with E. coli, strain H9049 compared to controls, however no differences in leukocyte numbers, neutrophil infiltration, or iron distribution   (MGI Ref ID J:95107)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Immunology, Inflammation and Autoimmunity Research

Metabolism Research
Iron Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Lcn2tm1Aade
Allele Name targeted mutation 1, Alan Aderem
Allele Type Targeted (Null/Knockout)
Common Name(s) Lcn2-;
Strain of Origin129P2/OlaHsd
Gene Symbol and Name Lcn2, lipocalin 2
Chromosome 2
Gene Common Name(s) 24p3; AW212229; MSFI; NGAL; Sip24; expressed sequence AW212229;
Molecular Note A neo replaced coding exons 2-5. Absence of transcript was demonstrated by Northern blot analysis of mutant peritoneal macrophages. Immunoblot of mutant cell lysates confirmed the lack of protein. [MGI Ref ID J:95107]

Genotyping

Genotyping Information

Genotyping Protocols

Lcn2tm1Aade, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Flo TH; Smith KD; Sato S; Rodriguez DJ; Holmes MA; Strong RK; Akira S; Aderem A. 2004. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432(7019):917-21. [PubMed: 15531878]  [MGI Ref ID J:95107]

Additional References

Lcn2tm1Aade related

Cramer EP; Glenthoj A; Hager M; Juncker-Jensen A; Engelholm LH; Santoni-Rugiu E; Lund LR; Laerum OD; Cowland JB; Borregaard N. 2012. No effect of NGAL/lipocalin-2 on aggressiveness of cancer in the MMTV-PyMT/FVB/N mouse model for breast cancer. PLoS One 7(6):e39646. [PubMed: 22737251]  [MGI Ref ID J:187808]

Eller K; Schroll A; Banas M; Kirsch AH; Huber JM; Nairz M; Skvortsov S; Weiss G; Rosenkranz AR; Theurl I. 2013. Lipocalin-2 expressed in innate immune cells is an endogenous inhibitor of inflammation in murine nephrotoxic serum nephritis. PLoS One 8(7):e67693. [PubMed: 23861783]  [MGI Ref ID J:204293]

Fischbach MA; Lin H; Zhou L; Yu Y; Abergel RJ; Liu DR; Raymond KN; Wanner BL; Strong RK; Walsh CT; Aderem A; Smith KD. 2006. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2. Proc Natl Acad Sci U S A 103(44):16502-7. [PubMed: 17060628]  [MGI Ref ID J:115597]

Fritsche G; Nairz M; Libby SJ; Fang FC; Weiss G. 2012. Slc11a1 (Nramp1) impairs growth of Salmonella enterica serovar typhimurium in macrophages via stimulation of lipocalin-2 expression. J Leukoc Biol 92(2):353-9. [PubMed: 22706314]  [MGI Ref ID J:186255]

Guo H; Bazuine M; Jin D; Huang MM; Cushman SW; Chen X. 2013. Evidence for the regulatory role of lipocalin 2 in high-fat diet-induced adipose tissue remodeling in male mice. Endocrinology 154(10):3525-38. [PubMed: 23885013]  [MGI Ref ID J:203290]

Guo H; Jin D; Zhang Y; Wright W; Bazuine M; Brockman DA; Bernlohr DA; Chen X. 2010. Lipocalin-2 deficiency impairs thermogenesis and potentiates diet-induced insulin resistance in mice. Diabetes 59(6):1376-85. [PubMed: 20332347]  [MGI Ref ID J:169355]

Guo H; Zhang Y; Brockman DA; Hahn W; Bernlohr DA; Chen X. 2012. Lipocalin 2 deficiency alters estradiol production and estrogen receptor signaling in female mice. Endocrinology 153(3):1183-93. [PubMed: 22234464]  [MGI Ref ID J:182562]

Jang E; Kim JH; Lee S; Kim JH; Seo JW; Jin M; Lee MG; Jang IS; Lee WH; Suk K. 2013. Phenotypic polarization of activated astrocytes: the critical role of lipocalin-2 in the classical inflammatory activation of astrocytes. J Immunol 191(10):5204-19. [PubMed: 24089194]  [MGI Ref ID J:206340]

Jang E; Lee S; Kim JH; Kim JH; Seo JW; Lee WH; Mori K; Nakao K; Suk K. 2013. Secreted protein lipocalin-2 promotes microglial M1 polarization. FASEB J 27(3):1176-90. [PubMed: 23207546]  [MGI Ref ID J:196978]

Jeon S; Jha MK; Ock J; Seo J; Jin M; Cho H; Lee WH; Suk K. 2013. Role of lipocalin-2-chemokine axis in the development of neuropathic pain following peripheral nerve injury. J Biol Chem 288(33):24116-27. [PubMed: 23836894]  [MGI Ref ID J:203453]

Jin D; Guo H; Bu SY; Zhang Y; Hannaford J; Mashek DG; Chen X. 2011. Lipocalin 2 is a selective modulator of peroxisome proliferator-activated receptor-gamma activation and function in lipid homeostasis and energy expenditure. FASEB J 25(2):754-64. [PubMed: 20974668]  [MGI Ref ID J:170748]

Jun LS; Siddall CP; Rosen ED. 2011. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance. Am J Physiol Endocrinol Metab 301(5):E825-35. [PubMed: 21771968]  [MGI Ref ID J:182182]

Layoun A; Huang H; Calve A; Santos MM. 2012. Toll-Like Receptor Signal Adaptor Protein MyD88 Is Required for Sustained Endotoxin-Induced Acute Hypoferremic Response in Mice. Am J Pathol 180(6):2340-50. [PubMed: 22497726]  [MGI Ref ID J:184700]

Lee S; Kim JH; Kim JH; Seo JW; Han HS; Lee WH; Mori K; Nakao K; Barasch J; Suk K. 2011. Lipocalin-2 Is a Chemokine Inducer in the Central Nervous System: ROLE OF CHEMOKINE LIGAND 10 (CXCL10) IN LIPOCALIN-2-INDUCED CELL MIGRATION. J Biol Chem 286(51):43855-70. [PubMed: 22030398]  [MGI Ref ID J:178754]

Leng X; Ding T; Lin H; Wang Y; Hu L; Hu J; Feig B; Zhang W; Pusztai L; Symmans WF; Wu Y; Arlinghaus RB. 2009. Inhibition of lipocalin 2 impairs breast tumorigenesis and metastasis. Cancer Res 69(22):8579-84. [PubMed: 19887608]  [MGI Ref ID J:154442]

Mucha M; Skrzypiec AE; Schiavon E; Attwood BK; Kucerova E; Pawlak R. 2011. Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation. Proc Natl Acad Sci U S A 108(45):18436-41. [PubMed: 21969573]  [MGI Ref ID J:180098]

Nairz M; Theurl I; Schroll A; Theurl M; Fritsche G; Lindner E; Seifert M; Crouch ML; Hantke K; Akira S; Fang FC; Weiss G. 2009. Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood 114(17):3642-51. [PubMed: 19700664]  [MGI Ref ID J:153840]

Nocon AL; Ip JP; Terry R; Lim SL; Getts DR; Muller M; Hofer MJ; King NJ; Campbell IL. 2014. The bacteriostatic protein lipocalin 2 is induced in the central nervous system of mice with west Nile virus encephalitis. J Virol 88(1):679-89. [PubMed: 24173226]  [MGI Ref ID J:205207]

Rathore KI; Berard JL; Redensek A; Chierzi S; Lopez-Vales R; Santos M; Akira S; David S. 2011. Lipocalin 2 plays an immunomodulatory role and has detrimental effects after spinal cord injury. J Neurosci 31(38):13412-9. [PubMed: 21940434]  [MGI Ref ID J:177126]

Saiga H; Nishimura J; Kuwata H; Okuyama M; Matsumoto S; Sato S; Matsumoto M; Akira S; Yoshikai Y; Honda K; Yamamoto M; Takeda K. 2008. Lipocalin 2-dependent inhibition of mycobacterial growth in alveolar epithelium. J Immunol 181(12):8521-7. [PubMed: 19050270]  [MGI Ref ID J:142063]

Schroll A; Eller K; Feistritzer C; Nairz M; Sonnweber T; Moser PA; Rosenkranz AR; Theurl I; Weiss G. 2012. Lipocalin-2 ameliorates granulocyte functionality. Eur J Immunol 42(12):3346-57. [PubMed: 22965758]  [MGI Ref ID J:190529]

Skrzypiec AE; Shah RS; Schiavon E; Baker E; Skene N; Pawlak R; Mucha M. 2013. Stress-induced lipocalin-2 controls dendritic spine formation and neuronal activity in the amygdala. PLoS One 8(4):e61046. [PubMed: 23593384]  [MGI Ref ID J:200578]

Srinivasan G; Aitken JD; Zhang B; Carvalho FA; Chassaing B; Shashidharamurthy R; Borregaard N; Jones DP; Gewirtz AT; Vijay-Kumar M. 2012. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis. J Immunol 189(4):1911-9. [PubMed: 22786765]  [MGI Ref ID J:189756]

Warszawska JM; Gawish R; Sharif O; Sigel S; Doninger B; Lakovits K; Mesteri I; Nairz M; Boon L; Spiel A; Fuhrmann V; Strobl B; Muller M; Schenk P; Weiss G; Knapp S. 2013. Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes. J Clin Invest :. [PubMed: 23863624]  [MGI Ref ID J:201415]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together. Mice should be housed in a specific pathogen free (SPF) facility.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   04-JUN-14

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Under Development - Now Accepting Orders.
Estimated Available for Distribution Date: 01-SEP-14

Please note: You may now place orders for this strain although it is not yet ready for distribution. Estimated available for distribution dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for distribution depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain.

Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHeterozygous for Lcn2tm1Aade  
$232.00Female or MaleHomozygous for Lcn2tm1Aade  
Price per Pair (US dollars $)Pair Genotype
$464.00Heterozygous for Lcn2tm1Aade x Heterozygous for Lcn2tm1Aade  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Lcn2tm1Aade  
$301.60Female or MaleHomozygous for Lcn2tm1Aade  
Price per Pair (US dollars $)Pair Genotype
$603.20Heterozygous for Lcn2tm1Aade x Heterozygous for Lcn2tm1Aade  

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Under Development - Now Accepting Orders The strain development process (i.e. importation, rederivation, and colony expansion) usually takes six to nine months.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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