Strain Detail Sheet

Strain Name    :

STOCK Gsntm1Djk/Mmnc

Stock Number :

000133-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Gsntm1Djk
Name: targeted mutation 1, David J Kwiatkowski
Alteration at locus: Knockout
Gene Symbol: Gsn
Name: gelsolin
Chromosome: 2
Alteration at locus: Knockout

Genetic Alterations:
A neo cassette was inserted into exon 4.

Genotype Determination:

ES Cell Line: J1

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Many cells of the mice have motility defects, including neutrophils, osteoclasts, neurons.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Gsntm1Djk/Gsntm1Djk
        either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
  • mortality/aging
    • premature death (MGI Ref ID J:52545)
      • not viable on either a "pure" BALB/c or C57BL/6 background
  • immune system phenotype
    • abnormal immune system physiology (MGI Ref ID J:24346)
      • abnormal osteoclast physiology (MGI Ref ID J:60625)
        • reduced stimulation of osteoclast migration above basal levels
      • decreased inflammatory response (MGI Ref ID J:24346)
        • neutrophile recruitment to inflammatory sites half normal
      • impaired neutrophil chemotaxis (MGI Ref ID J:24346)
        • much slower neutrophil migration rates in chemotaxis tests
      • impaired neutrophil recruitment (MGI Ref ID J:24346)
        • neutrophil recruitment to inflammatory sites half normal
    • abnormal osteoclast differentiation (MGI Ref ID J:60625)
      • podosomes not observed
      • F-actin organized in web-like structures or is diffusely distributed
      • osteopontin fails to cause an increase in F-actin organization into podosomes
    • increased leukocyte cell number (MGI Ref ID J:24346)
      • increased t otal leukocyte count in peripheral blood
      • increased neutrophil cell number (MGI Ref ID J:24346)
        • higher proportion of neutrophils in peripheral blood
  • homeostasis/metabolism phenotype
    • abnormal platelet physiology (MGI Ref ID J:24346)
      • abnormal platelet activation
      • 13% higher resting actin filament content but F-actin levels are similar to controls after activation
    • abnormal wound healing (MGI Ref ID J:24346)
      • dermal fibroblasts more active than controls in contracting collagen gels, embryonic fibroblasts slower
    • increased bleeding time (MGI Ref ID J:24346)
      • tail bleeding times 2x normal
      • persistent, slow bleeding and re bleeding after initial cessation
  • skeleton phenotype
    • abnormal skeleton morphology (MGI Ref ID J:60625)
      • abnormal long bone diaphysis morphology (MGI Ref ID J:60625)
        • increased diaphyseal thickness but no long bone deformities
      • abnormal long bone epiphyseal plate morphology (MGI Ref ID J:60625)
        • chondrocytes of epiphyseal growth plates reduced in number and somewhat disorganized
        • expanded matrix
      • abnormal osteoclast differentiation (MGI Ref ID J:60625)
        • podosomes not observed
        • F-actin organized in web-like structures or is diffusely distributed
        • osteopontin fails to cause an increase in F-actin organization into podosomes
      • increased compact bone thickness (MGI Ref ID J:60625)
        • in tibial and femoral diaphysis at 14 weeks of age
      • osteopetrosis (MGI Ref ID J:60625)
        • increased bone mass
    • abnormal skeleton physiology (MGI Ref ID J:60625)
      • abnormal bone remodeling (MGI Ref ID J:60625)
        • abnormal osteoclast physiology (MGI Ref ID J:60625)
          • reduced stimulation of osteoclast migration above basal levels
  • hematopoietic system phenotype
    • abnormal osteoclast differentiation (MGI Ref ID J:60625)
      • podosomes not observed
      • F-actin organized in web-like structures or is diffusely distributed
      • osteopontin fails to cause an increase in F-actin organization into podosomes
    • abnormal platelet physiology (MGI Ref ID J:24346)
      • abnormal platelet activation
      • 13% higher resting actin filament content but F-actin levels are similar to controls after activation
    • increased leukocyte cell number (MGI Ref ID J:24346)
      • increased total leukocyte count in peripheral blood
      • increased neutrophil cell number (MGI Ref ID J:24346)
        • higher proportion of neutrophils in peripheral blood
  • limbs/digits/tail phenotype
    • abnormal long bone diaphysis morphology (MGI Ref ID J:60625)
      • increased diaphyseal thickness but no long bone deformities
    • abnormal long bone epiphyseal plate morphology (MGI Ref ID J:606 25)
      • chondrocytes of epiphyseal growth plates reduced in number and somewhat disorganized
      • expanded matrix
Gsntm1Djk/Gsntm1Djk
        involves: 129S4/SvJae * BALB/c
  • mortality/aging
    • complete lethality throughout fetal growth and development (MGI Ref ID J:64868)
      • after the N6 backcross to BALB/c, embryonic lethality is seen between E17.5 and birth; on a mixed 129Sv/BALB/c background, homozygotes survive
  • endocrine/exocrine gland phenotype
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:64868)
      • lack terminal end buds at 4 weeks of age but only seen when the genetic background is greater than 50% 129/Sv
      • ductal epithelial tree remains at 4 week stage in 8 week old mice
      • lack of terminal branching persists as long as the mice remain virgin
    • abnormal mammary gland growth during pregnancy (MGI Ref ID J:64868)
      • by mid gestation, mammary gland development is comparable to controls in early pregnancy
      • development continues but with delays
      • slower growth of mammary epithelium
      • mammary glands indistinguishable from controls during lactation
      • involution of mammary gland after weaning is normal
  • reproductive system phenotype
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:64868)
      • lack terminal end buds at 4 weeks of age but only seen when the genetic background is greater than 50% 129/Sv
      • ductal epithelial tree remains at 4 week stage in 8 week old mice
      • lack of terminal branching persists as long as the mice remain virgin
    • abnormal mammary gland growth during pregnancy (MGI Ref ID J:64868)
      • by mid gestation, mammary gland development is comparable to controls in early pregnancy
      • development continues b ut with delays
      • slower growth of mammary epithelium
      • mammary glands indistinguishable from controls during lactation
      • involution of mammary gland after weaning is normal
  • integument phenotype
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:64868)
      • lack terminal end buds at 4 weeks of age but only seen when the genetic background is greater than 50% 129/Sv
      • ductal epithelial tree remains at 4 week stage in 8 week old mice
      • lack of terminal branching persists as long as the mice remain virgin
    • abnormal mammary gland growth during pregnancy (MGI Ref ID J:64868)
      • by mid gestation, mammary gland development is comparable to controls in early pregnancy
      • development continues but with delays
      • slower growth of mammary epithelium
      • mammary glands indistinguishable from controls during lactation
      • involution of mammary gland after weaning is normal
Gsntm1Djk/Gsntm1Djk
        involves: 129S4/SvJae * C57BL/6
  • nervous system phenotype
    • abnormal nervous system electrophysiology (MGI Ref ID J:52545)
      • nerve depolarization results in increased Ca+2 in synaptosomes
    • increased susceptibility to ischemic brain injury (MGI Ref ID J:52545)
      • increased Ca+2 mediated proteolysis in ischemic brains
      • increased cerebral infarction size (MGI Ref ID J:52545)
        • experimental brain ischemia leads to large infarct size
  • cardiovascular system phenotype
    • abnormal pulmonary circulation (MGI Ref ID J:94614)
      • vascular permeability to proteins increased in lungs
    • increased vascular permeability (MGI Ref ID J:94614)
      • vascular permeability to proteins increased in lungs
      • 18x increase in protein concentration in baseline lung lavage
      • pulmonary artery ischemia causes slower increase in protein permeability than seen in controls
  • respiratory system phenotype
    • abnormal pulmonary circulation (MGI Ref ID J:94614)
      • vascular permeability to proteins increased in lungs
  • homeostasis/metabolism phenotype
    • increased susceptibility to ischemic brain injury (MGI Ref ID J:52545)
      • increased Ca+2 mediated proteolysis in ischemic brains
      • increased cerebral infarction size (MGI Ref ID J:52545)
        • experimental brain ischemia leads to large infarct size

Strain of Origin: STOCK (mixed B6,129,BALB/c)

Strain genetic background: mixed

Strain Development: See primary reference.

Research Applications

  • Apoptosis
  • Cancer
  • Cell Biology
  • Developmental Biology
  • Hematology
  • Immunology and Inflammation-
  • Models for Human Disease
  • Neurobiology
  • Research Tools

Strain Origin

Donor: David Kwiatkowski, Ph.D., Brigham and Women's Hospital

Primary Reference:

  • Witke W, Sharpe AH, Hartwig JH, Azuma T, Stossel TP, Kwiatkowski DJ. Hemostatic, inflammatory, and fibroblast responses are blunted in mice lacking gelsolin. Cell. 1995 Apr 7;81(1):41-51. (Medline PMID: 7720072)
  • Lu M, Witke W, Kwiatkowski DJ, Kosik KS. Delayed retraction of filopodia in gelsolin null mice. J Cell Biol. 1997 Sep 22;138(6):1279-87. (Medline PMID: 9298983)
  • CKothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ, Williams LT. Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis. Science. 1997 Oct 10;278(5336):294-8. (Medline PMID: 9323209)

Colony and Husbandry Information

Special Considerations

None

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.

Appearance

Coat color:

Other:

Breeding

MMRRC Breeding System: Intra-strain mating of homozygotes

Breeding Scheme(s):

  • Homozygous male x homozygous female

Generation: Unknown

Overall Breeding Performance: Good

Reproductive Statistics

Viability and Fertility:FemaleMale
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes

Age Reproductive Decline: Unknown Unknown

Average litter size: 6 - 8

Recommended wean age: 3 weeks

Order Request Information

Availability Level

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Conditions of Distribution [Including applicable technology transfer agreements]

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.

Fees

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.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # - Description Distribution
Fee/unit (US $)
Units Notes
000133-UNC-RESUSLitter recovered from cryo-archive
$2,022.00
Non-Profit
Litter Recovered litter1; additional fees for any special requests.

1 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.

2 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.

3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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