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 System Homozygote x Homozygote         (Female x Male)   15-MAY-08 Species laboratory mouse Generation N5+N1F3 (22-JAN-09)   Donating Investigator Richard Cummings,   University of Oklahoma

Description
Homozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavoiral abnormalities. No gene product (mRNA or protein) is detected by in situ hybridization of tibia bones sections from embryonic day 16.4 mice or by immunohistological staining of fetal skin. Homozygotes have an impaired acute inflammation response. Initial inflammatory infiltrate cell recruitment is normal, but four days after intraperitoneal injection of thioglycollate, mutant mice have a four-fold lower number of recruited granulocytes. Mutant mice have impaired chondrocyte differentiation during long bone development. Fewer hypertrophic chondrocytes but more empty lacunae and condensed chondrocytes are found in the chondrovascular junction. Chondrocytes, cartilage matrix and lacunae are morphologically abnormal. Carbon tetrachloride-induced liver fibrosis results in reduced collagen deposition when compared to wildtype controls. Mutant mice also display defective myofibroblast activation. This mutant mouse strain may be useful in studies of bone development, endochondral ossification, inflammatory response, and liver fibrosis.

This strain was transferred from the Consortium for Functional Glycomics strain collection.

It has been the experience of The Jackson Laboratory that these mice experience a transient period of hairloss between the ages of 2-6 weeks, with full hair growth returning by six weeks of age. Analysis of skin sections reveals a pathology similar to what is seen in C57BL/6 alopecia and movement of these alleles onto the C57BL/6J background may have exacerbated this phenotype.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 3.7kb of sequence that includes exons 2, 3 and 4. The construct was electroporated into WW6 embryonic stem (ES) cells (derived from 129/Sv, C57BL/6, SJL mixed background mice). Correctly targeted ES cells were injected into outbred MF-1 blastocysts. The resulting chimeric male animals were crossed to 129 female mice. Heterozygotes were crossed to generate homozygotes. The mice were then bred to mice homozygous for a targeted mutation of Lgals1, and he double mutant strain was backcrossed to C57BL/6 for 5 generations. Upon arrival at The Jackson Laboratory, the Lgals1mutation was removed by selective breeding; therefore this strain carries only the Lgals3^tm1Poi allele.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Lgals3^tm1Poi allele

006354

B6.Cg-Lgals3tm1Poi Lgals1tm1Rob/J

View Strains carrying   Lgals3^tm1Poi     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Lgals3^tm1Poi/Lgals3^tm1Poi

        involves: 129 * 129/Sv * C57BL/6J * SJL

• life span-post-weaning/aging
• *normal* life span-post-weaning/aging (MGI Ref ID J:47227)
  • mice exhibit a normal lifespan
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:47227)
  • mice exhibit normal reproduction
• skin/coat/nails phenotype
• *normal* skin/coat/nails phenotype (MGI Ref ID J:47227)
  • mice exhibit normal skin structure

Lgals3^tm1Poi/Lgals3^tm1Poi

        involves: 129/Sv * C57BL/6 * SJL

• life span-post-weaning/aging
• increased sensitivity to induced morbidity/mortality (MGI Ref ID J:131407)
  • mice infected with S. pneumoniae exhibit high mortality after 24 hours
• immune system phenotype
• abnormal macrophage physiology (MGI Ref ID J:131971)
  • macrophage activation by IL-4 and IL-13 stimulation Is impaired
  • however, macrophage activation by IFN-gamma and LPS is normal
• impaired macrophage phagocytosis (MGI Ref ID J:131407)
  • phagocytosis of apoptotic neutrophils by bone marrow-derived macrophages is impaired
  • however, phagocytosis of S. pneumonia is normal
• impaired macrophage recruitment (MGI Ref ID J:131971)
  • when stimulated by IL-4 and IL-13
• impaired neutrophil recruitment (MGI Ref ID J:131407)
  • 15 hours after infection with S. pneumoniae
  • however, myeloperoxidase activity is similar to in wild-type mice 15 hours after infection with S. pneumoniae
• increased interleukin-6 secretion (MGI Ref ID J:131407)
  • 15 hours after infection with S. pneumoniae, IL-6 concentration in bronchoalveolar lavage is increased compared to in wild-type mice
• increased susceptibility to bacterial infection (MGI Ref ID J:131407)
  • mice infected with S. pneumoniae exhibit high mortality after 24 hours
  • after 15 hours, mice infected with S. pneumoniae exhibit increased cell infiltrate but decreased total cell counts in the lungs and develop severe pneumonia with increased lung injury and septicemia compared to wild-type mice
  • after 15 hours, mice infected with S. pneumoniae exhibit a 450-fold increase in bacterial load compared to wild-type mice and blood cultures indicate 100 % bacteremia compared to 30% in wild-type mice
• increased tumor necrosis factor secretion (MGI Ref ID J:131407)
  • 15 hours after infection with S. pneumoniae, TNF-alpha concentration in bronchoalveolar lavage is increased compared to in wild-type mice
• lung inflammation (MGI Ref ID J:131407)
  • after 15 hours, mice infected with S. pneumoniae exhibit increased cell infiltrate in the lungs and develop severe pneumonia with increased lung injury and septicemia compared to wild-type mice
• sepsis (MGI Ref ID J:131407)
  • after 15 hours, mice infected with S. pneumoniae exhibit septicemia unlike wild-type mice
• skeleton phenotype
• abnormal long bone epiphyseal plate morphology (MGI Ref ID J:66902)
  • unlike in wild-type mice, a large zone of empty lacunae is observed between the last row of hypertrophic cells and the vascular invasion front
• abnormal long bone hypertrophic chondrocyte zone (MGI Ref ID J:66902)
  • chondrocytes within the hypertrophic zone are larger and more vacuolated than in wild-type mice
  • mice exhibit an increased number of nonhypertrophic cells in the late hyprtrophic zone compared to in wild-type mice
  • chondrocytes in the zone contain unusually large intracellular glycogen aggregates
• decreased width of hypertrophic chondrocyte zone (MGI Ref ID J:66902)
  • the hypertrophic zone is reduced in size and contains 20% fewer hypertrophic cells than in wild type mice
• renal/urinary system phenotype
• abnormal kidney physiology (MGI Ref ID J:131371)
  • mice exhibit less renal fibrosis following unilateral ureter obstruction (UUO) compared to wild-type mice
  • however, macrophage recruitment and cytokine production induced by UUO is normal
• respiratory system phenotype
• lung inflammation (MGI Ref ID J:131407)
  • after 15 hours, mice infected with S. pneumoniae exhibit increased cell infiltrate in the lungs and develop severe pneumonia with increased lung injury and septicemia compared to wild-type mice
• homeostasis/metabolism phenotype
• decreased susceptibility to injury (MGI Ref ID J:131371)
  • mice exhibit less renal fibrosis following unilateral ureter obstruction (UUO) compared to wild-type mice
  • however, macrophage recruitment and cytokine production induced by UUO is normal
• limbs/digits/tail phenotype
• abnormal long bone epiphyseal plate morphology (MGI Ref ID J:66902)
  • unlike in wild-type mice, a large zone of empty lacunae is observed between the last row of hypertrophic cells and the vascular invasion front
• abnormal long bone hypertrophic chondrocyte zone (MGI Ref ID J:66902)
  • chondrocytes within the hypertrophic zone are larger and more vacuolated than in wild-type mice
  • mice exhibit an increased number of nonhypertrophic cells in the late hyprtrophic zone compared to in wild-type mice
  • chondrocytes in the zone contain unusually large intracellular glycogen aggregates
• decreased width of hypertrophic chondrocyte zone (MGI Ref ID J:66902)
  • the hypertrophic zone is reduced in size and contains 20% fewer hypertrophic cells than in wild type mice

Lgals3^tm1Poi/Lgals3^tm1Poi

        involves: 129/Sv * C57BL/6 * MF1 * SJL

• hematopoietic system phenotype
• decreased granulocyte number (MGI Ref ID J:110422)
  • while recruitment of granulocytes following treatment with thioglycolate is normal, granulocyte numbers 3 to 4 days after treatment are reduced 4-fold compared to in wild-type mice
  • however, granulocyte apoptosis rates and phagocytosis of apoptotic granulocytes are normal
• immune system phenotype
• decreased granulocyte number (MGI Ref ID J:110422)
  • while recruitment of granulocytes following treatment with thioglycolate is normal, granulocyte numbers 3 to 4 days after treatment are reduced 4-fold compared to in wild-type mice
  • however, granulocyte apoptosis rates and phagocytosis of apoptotic granulocytes are normal

View Research Applications

Research Applications

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

Developmental Biology Research
Skeletal Defects

Immunology and Inflammation Research
Inflammation

Genes & Alleles

Gene & Allele Information

Allele Symbol		Lgals3tm1Poi
Allele Name		targeted mutation 1, Francoise Poirier
Allele Type		Targeted (knock-out)
Common Name(s)		GaL3-; galectin 3<->;
Mutation Made By		Richard Cummings,   University of Oklahoma
Strain of Origin		STOCK 129/Sv and C57BL/6J and SJL
ES Cell Line Name		WW6
ES Cell Line Strain		STOCK 129/Sv and C57BL/6J and SJL
Gene Symbol and Name		Lgals3, lectin, galactose binding, soluble 3
Chromosome		14
Gene Common Name(s)		CBP35; GAL3; GALBP; GALIG; L-34; LGALS2; MAC2; MGC105387; Mac-2; gal-3; galectin-3;
Molecular Note		3.7kb of sequence, encompassing exons 2 through 4, was replaced via the insertion of a neomycin selection cassette. Immunostaining of fetal skin showed an absence of protein in homozygous mutant embryos. [MGI Ref ID J:47227]

Genotyping

Genotyping Information

Genotyping Protocols

Lgals3^tm1Poi, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Colnot C; Fowlis D; Ripoche MA; Bouchaert I; Poirier F. 1998. Embryonic implantation in galectin 1/galectin 3 double mutant mice. Dev Dyn 211(4):306-13. [PubMed: 9566950]  [MGI Ref ID J:47227]

Additional References

Lgals3^tm1Poi related

Breuilh L; Vanhoutte F; Fontaine J; van Stijn CM; Tillie-Leblond I; Capron M; Faveeuw C; Jouault T; van Die I; Gosset P; Trottein F. 2007. Galectin-3 modulates immune and inflammatory responses during helminthic infection: impact of galectin-3 deficiency on the functions of dendritic cells. Infect Immun 75(11):5148-57. [PubMed: 17785480]  [MGI Ref ID J:126353]

Chiu MG; Johnson TM; Woolf AS; Dahm-Vicker EM; Long DA; Guay-Woodford L; Hillman KA; Bawumia S; Venner K; Hughes RC; Poirier F; Winyard PJ. 2006. Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease. Am J Pathol 169(6):1925-38. [PubMed: 17148658]  [MGI Ref ID J:116210]

Colnot C; Ripoche MA; Milon G; Montagutelli X; Crocker PR; Poirier F. 1998. Maintenance of granulocyte numbers during acute peritonitis is defective in galectin-3-null mutant mice. Immunology 94(3):290-6. [PubMed: 9767409]  [MGI Ref ID J:110422]

Colnot C; Ripoche MA; Scaerou F; Foulis D; Poirier F. 1996. Galectins in mouse embryogenesis. Biochem Soc Trans 24(1):141-6. [PubMed: 8674632]  [MGI Ref ID J:31899]

Colnot C; Sidhu SS; Balmain N; Poirier F. 2001. Uncoupling of chondrocyte death and vascular invasion in mouse galectin 3 null mutant bones. Dev Biol 229(1):203-14. [PubMed: 11133164]  [MGI Ref ID J:66902]

Delacour D; Koch A; Ackermann W; Eude-Le Parco I; Elsasser HP; Poirier F; Jacob R. 2008. Loss of galectin-3 impairs membrane polarisation of mouse enterocytes in vivo. J Cell Sci 121(Pt 4):458-65. [PubMed: 18211959]  [MGI Ref ID J:138282]

Farnworth SL; Henderson NC; Mackinnon AC; Atkinson KM; Wilkinson T; Dhaliwal K; Hayashi K; Simpson AJ; Rossi AG; Haslett C; Sethi T. 2008. Galectin-3 reduces the severity of pneumococcal pneumonia by augmenting neutrophil function. Am J Pathol 172(2):395-405. [PubMed: 18202191]  [MGI Ref ID J:131407]

Henderson NC; Mackinnon AC; Farnworth SL; Kipari T; Haslett C; Iredale JP; Liu FT; Hughes J; Sethi T. 2008. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol 172(2):288-98. [PubMed: 18202187]  [MGI Ref ID J:131371]

Henderson NC; Mackinnon AC; Farnworth SL; Poirier F; Russo FP; Iredale JP; Haslett C; Simpson KJ; Sethi T. 2006. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Natl Acad Sci U S A 103(13):5060-5. [PubMed: 16549783]  [MGI Ref ID J:107656]

MacKinnon AC; Farnworth SL; Hodkinson PS; Henderson NC; Atkinson KM; Leffler H; Nilsson UJ; Haslett C; Forbes SJ; Sethi T. 2008. Regulation of alternative macrophage activation by galectin-3. J Immunol 180(4):2650-8. [PubMed: 18250477]  [MGI Ref ID J:131971]

Nachtigal M; Ghaffar A; Mayer EP. 2008. Galectin-3 gene inactivation reduces atherosclerotic lesions and adventitial inflammation in ApoE-deficient mice. Am J Pathol 172(1):247-55. [PubMed: 18156214]  [MGI Ref ID J:130923]

Oakley MS; Majam V; Mahajan B; Gerald N; Anantharaman V; Ward JM; Faucette LJ; McCutchan TF; Zheng H; Terabe M; Berzofsky JA; Aravind L; Kumar S. 2009. Pathogenic roles of CD14, galectin-3, and OX40 during experimental cerebral malaria in mice. PLoS One 4(8):e6793. [PubMed: 19710907]  [MGI Ref ID J:152399]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   15-MAY-08
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - 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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phone:	207-288-6470
fax:	207-288-6655

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