Strain Name:

B6;129S7-Srctm1Sor/J

Stock Number:

002381

Availability:

Repository-Cryopreserved

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
GenerationN4
 
Donating Investigator Philippe Soriano,   Fred Hutchinson Cancer Research Center

Appearance
black
Related Genotype: a/a

white-bellied agouti
Related Genotype: Aw/?

Description
Mice homozygous for the Srctm1Sor targeted mutation display osteopetrosis. Homozygous mutant mice are approximately one-third the size of normal wildtype siblings. Incisors fail to erupt. In general, long bones are shorter in length and show a partial absence of bone marrow. Src has been implicated in development, but its role may be masked by other tyrosine kinases. No overt phenotype is found in brain or platelets, where it is most highly expressed. Mice heterozygous for the Srctm1Sor mutation have no apparent abnormalities.

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
   Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6;129 mixed background.
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Srctm1Sor allele
002277   B6.129S7-Srctm1Sor/J
View Strains carrying   Srctm1Sor     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Srctm1Sor/Srctm1Sor

        either: 129S7/SvEvBrd-Srctm1Sor or (involves: 129S7/SvEvBrd * C57BL/6J)
  • lethality-postnatal
  • postnatal lethality (MGI Ref ID J:67040)
    • at 3 weeks of age, only 19% of the mice are homozygous, suggesting a partial prenatal and/or partial early postnatal lethality
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:67040)
    • most animals died at 3-4 weeks of age if weaned; one-third of mice could be maintained past 5 weeks if not weaned and kept on a soft food diet
    • mice on a mixed background survive longer than mice on the inbred 129S7/SvEvBrd genetic background
  • growth/size phenotype
  • decreased body size (MGI Ref ID J:67040)
    • by 10-12 days of age, mice are noticeably smaller than controls
    • decreased body weight (MGI Ref ID J:67040)
      • mice grow more slowly and weigh about one-third to one-half as much as controls
  • skeleton phenotype
  • abnormal bone structure (MGI Ref ID J:67040)
    • abnormal bone marrow cavity morphology (MGI Ref ID J:67040)
      • the bone marrow cavity was filled with little room for hematopoietic elements
    • abnormal bone marrow morphology (MGI Ref ID J:67040)
      • partial absence of bone marrow
    • abnormal cancellous bone morphology (MGI Ref ID J:67040)
      • there is a widening and extension of the trabecular bone deep into the distal metaphysis and diaphysis
      • the central trabeculae consist of calcified cartilage
    • decreased cortical bone thickness (MGI Ref ID J:67040)
      • cortical bone is thinner and disorganized
    • osteopetrosis (MGI Ref ID J:67040)
      • noted in calvarium, nasal turbinates, facial bones, mandible, tibia and femurs; obvious in long bones at P10 and in the crainial bones at birth
  • abnormal craniofacial bone morphology (MGI Ref ID J:67040)
    • facial bones are thickened by fibrous and osseous tissue proliferation and lack of bone resorbtion
    • smaller airway lumina are present due to abnormal facial bone morphology
  • abnormal long bone morphology (MGI Ref ID J:67040)
    • abnormal long bone diaphysis morphology (MGI Ref ID J:67040)
      • short diaphysis of the long bones
    • decreased length of long bones (MGI Ref ID J:67040)
      • long bones are shorter in length
  • decreased bone resorption (MGI Ref ID J:67040)
    • bone resorption is minimal to absent
  • delayed endochondral bone ossification (MGI Ref ID J:67040)
    • persistence of endochondrial primary spongiosa
  • increased long bone epiphyseal plate size (MGI Ref ID J:67040)
    • thickened growth plates in the long bones
  • pigmentation phenotype
  • diluted coat color (MGI Ref ID J:67040)
    • mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background
  • vision/eye phenotype
  • abnormal anterior eye segment morphology (MGI Ref ID J:67040)
    • at later ages, the eyes are frequently cloudy due to secreted material
  • delayed eyelid opening (MGI Ref ID J:67040)
  • hematopoietic system phenotype
  • *normal* hematopoietic system phenotype (MGI Ref ID J:67040)
    • normal red and white cell parameters are seen
    • normal platelet counts are seen
    • no evidence of hemorrhage or platelet dysfunction is seen; mice are capable of wound healing following tail or toe clipping
    • the liver and spleen are normal in size
    • parafollicular cells of the thyroid are normal
    • Kuppfer cells in the liver are normal in quantity and morphology
  • nervous system phenotype
  • *normal* nervous system phenotype (MGI Ref ID J:67040)
    • no microscopic brain lesions are apparent in multiple substructures
    • general brain architecture is normal and axon extension and fasciculation appear normal
  • immune system phenotype
  • increased inflammatory response (MGI Ref ID J:67040)
    • suppurative peridontal inflammation is seen in some animals
    • necrotic debris and acute inflammatory cells are sometimes seen within the lumen of the nasolacrimal duct
  • craniofacial phenotype
  • abnormal craniofacial bone morphology (MGI Ref ID J:67040)
    • facial bones are thickened by fibrous and osseous tissue proliferation and lack of bone resorbtion
    • smaller airway lumina are present due to abnormal facial bone morphology
  • abnormal head morphology (MGI Ref ID J:67040)
    • mice have a slightly domed head
    • abnormal tooth eruption (MGI Ref ID J:67040)
      • some molar teeth show partial eruption, but are crowded by osseous growth of the facial bones
      • failure of tooth eruption (MGI Ref ID J:67040)
        • incisor teeth are well developed, but fail to erupt through the gum
    • absent incisors (MGI Ref ID J:67040)
      • incisors are absent at 3 weeks of age
      • incisor teeth are well developed, but fail to erupt through the gum
    • broad head (MGI Ref ID J:67040)
      • mice have a broad face
  • skin/coat/nails phenotype
  • diluted coat color (MGI Ref ID J:67040)
    • mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background
  • limbs/digits/tail phenotype
  • abnormal limb morphology (MGI Ref ID J:67040)
    • enlarged, club-shaped extremities
  • abnormal long bone morphology (MGI Ref ID J:67040)
    • abnormal long bone diaphysis morphology (MGI Ref ID J:67040)
      • short diaphysis of the long bones
    • decreased length of long bones (MGI Ref ID J:67040)
      • long bones are shorter in length
View Research Applications

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

Srctm1Sor related

Cancer Research
Genes Regulating Growth and Proliferation
Oncogenes

Developmental Biology Research
Skeletal Defects (osteopetrosis)

Genes & Alleles

Gene & Allele Information

Allele Symbol Srctm1Sor
Allele Name targeted mutation 1, Philippe Soriano
Allele Type Targeted (knock-out)
Common Name(s) src-;
Mutation Made By Philippe Soriano,   Fred Hutchinson Cancer Research Center
Strain of Origin129S7/SvEvBrd-Hprt1
ES Cell Line NameAB2.1
ES Cell Line Strain129S7/SvEvBrd-Hprt1
Gene Symbol and Name Src, Rous sarcoma oncogene
Chromosome 2
Gene Common Name(s) ASV; AW259666; SRC1; c-SRC; expressed sequence AW259666; p60-Src; pp60c-src;
Molecular Note A neomycin cassette was inserted into the first coding exon. Northern blot analysis confirmed that no wild-type transcript was present in homozygous mice. No autophosphorylation activity corresponding to the encoded protein is detectable in homozygous mice. [MGI Ref ID J:67040]

Genotyping

Genotyping Information

Genotyping Protocols

Srctm1Sor, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Soriano P; Montgomery C; Geske R; Bradley A. 1991. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 64(4):693-702. [PubMed: 1997203]  [MGI Ref ID J:67040]

Additional References

Lowe C; Yoneda T; Boyce BF; Chen H; Mundy GR; Soriano P. 1993. Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts. Proc Natl Acad Sci U S A 90(10):4485-9. [PubMed: 7685105]  [MGI Ref ID J:11847]

Lowell CA; Niwa M; Soriano P; Varmus HE. 1996. Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis. Blood 87(5):1780-92. [PubMed: 8634424]  [MGI Ref ID J:31647]

Smith CL; Mittaud P; Prescott ED; Fuhrer C; Burden SJ. 2001. Src, Fyn, and Yes are not required for neuromuscular synapse formation but are necessary for stabilization of agrin-induced clusters of acetylcholine receptors. J Neurosci 21(9):3151-60. [PubMed: 11312300]  [MGI Ref ID J:70507]

Srctm1Sor related

Amling M; Neff L; Priemel M; Schilling AF; Rueger JM; Baron R. 2000. Progressive increase in bone mass and development of odontomas in aging osteopetrotic c-src-deficient mice Bone 27(5):603-10. [PubMed: 11062345]  [MGI Ref ID J:65368]

Arnaud L; Ballif BA; Forster E; Cooper JA. 2003. Fyn tyrosine kinase is a critical regulator of disabled-1 during brain development. Curr Biol 13(1):9-17. [PubMed: 12526739]  [MGI Ref ID J:109820]

Bakewell SJ; Nestor P; Prasad S; Tomasson MH; Dowland N; Mehrotra M; Scarborough R; Kanter J; Abe K; Phillips D; Weilbaecher KN. 2003. Platelet and osteoclast beta3 integrins are critical for bone metastasis. Proc Natl Acad Sci U S A 100(24):14205-10. [PubMed: 14612570]  [MGI Ref ID J:86702]

Ballif BA; Arnaud L; Cooper JA. 2003. Tyrosine phosphorylation of Disabled-1 is essential for Reelin-stimulated activation of Akt and Src family kinases. Brain Res Mol Brain Res 117(2):152-9. [PubMed: 14559149]  [MGI Ref ID J:115650]

Boyce BF; Chen H; Soriano P; Mundy GR. 1993. Histomorphometric and immunocytochemical studies of src-related osteopetrosis. Bone 14(3):335-40. [PubMed: 7689855]  [MGI Ref ID J:15781]

Boyce BF; Yoneda T; Lowe C; Soriano P; Mundy GR. 1992. Requirement of pp60c-src expression for osteoclasts to form ruffled borders and resorb bone in mice. J Clin Invest 90(4):1622-7. [PubMed: 1383278]  [MGI Ref ID J:111176]

Criscuoli ML; Nguyen M; Eliceiri BP. 2005. Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability. Blood 105(4):1508-14. [PubMed: 15486073]  [MGI Ref ID J:95907]

Davis ME; Cai H; McCann L; Fukai T; Harrison DG. 2003. Role of c-Src in regulation of endothelial nitric oxide synthase expression during exercise training. Am J Physiol Heart Circ Physiol 284(4):H1449-53. [PubMed: 12595302]  [MGI Ref ID J:108047]

Eliceiri BP; Paul R; Schwartzberg PL; Hood JD; Leng J; Cheresh DA. 1999. Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability. Mol Cell 4(6):915-24. [PubMed: 10635317]  [MGI Ref ID J:59158]

Falcone RA Jr; Shin CE; Erwin CR; Warner BW. 1999. The adaptive intestinal response to massive enterectomy is preserved in c-SRC-deficient mice. J Pediatr Surg 34(5):800-4. [PubMed: 10359184]  [MGI Ref ID J:57179]

Greenberg RS; Bernstein AM; Benezra M; Gelman IH; Taliana L; Masur SK. 2006. FAK-dependent regulation of myofibroblast differentiation. FASEB J 20(7):1006-8. [PubMed: 16585062]  [MGI Ref ID J:111499]

Guy CT; Muthuswamy SK; Cardiff RD; Soriano P; Muller WJ. 1994. Activation of the c-Src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev 8(1):23-32. [PubMed: 7507074]  [MGI Ref ID J:72125]

Kim H; Laing M; Muller W. 2005. c-Src-null mice exhibit defects in normal mammary gland development and ERalpha signaling. Oncogene 24(36):5629-36. [PubMed: 16007215]  [MGI Ref ID J:100783]

Klinghoffer RA; Sachsenmaier C; Cooper JA; Soriano P. 1999. Src family kinases are required for integrin but not PDGFR signal transduction. EMBO J 18(9):2459-71. [PubMed: 10228160]  [MGI Ref ID J:54973]

Koh AJ; Demiralp B; Neiva KG; Hooten J; Nohutcu RM; Shim H; Datta NS; Taichman RS; McCauley LK. 2005. Cells of the osteoclast lineage as mediators of the anabolic actions of parathyroid hormone in bone. Endocrinology 146(11):4584-96. [PubMed: 16081645]  [MGI Ref ID J:129838]

Lowe C; Yoneda T; Boyce BF; Chen H; Mundy GR; Soriano P. 1993. Osteopetrosis in Src-deficient mice is due to an autonomous defect of osteoclasts. Proc Natl Acad Sci U S A 90(10):4485-9. [PubMed: 7685105]  [MGI Ref ID J:11847]

Lowell CA; Niwa M; Soriano P; Varmus HE. 1996. Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis. Blood 87(5):1780-92. [PubMed: 8634424]  [MGI Ref ID J:31647]

Luton F; Verges M; Vaerman JP; Sudol M; Mostov KE. 1999. The SRC family protein tyrosine kinase p62yes controls polymeric IgA transcytosis in vivo. Mol Cell 4(4):627-32. [PubMed: 10549294]  [MGI Ref ID J:120157]

Miyata A; Baba O; Oda T; Ishikawa I; Takano Y. 2007. Diverse effects of c-src deficiency on molar tooth development and eruption in mice. Arch Histol Cytol 70(1):63-78. [PubMed: 17558145]  [MGI Ref ID J:124387]

Nakamura I; Rodan GA; Duong le T. 2003. Distinct roles of p130Cas and c-Cbl in adhesion-induced or macrophage colony-stimulating factor-mediated signaling pathways in prefusion osteoclasts. Endocrinology 144(11):4739-41. [PubMed: 12959979]  [MGI Ref ID J:105618]

Parravicini V; Gadina M; Kovarova M; Odom S; Gonzalez-Espinosa C; Furumoto Y; Saitoh S; Samelson LE; O'Shea JJ; Rivera J. 2002. Fyn kinase initiates complementary signals required for IgE-dependent mast cell degranulation. Nat Immunol 3(8):741-8. [PubMed: 12089510]  [MGI Ref ID J:109153]

Paul R; Zhang ZG; Eliceiri BP; Jiang Q; Boccia AD; Zhang RL; Chopp M; Cheresh DA. 2001. Src deficiency or blockade of Src activity in mice provides cerebral protection following stroke. Nat Med 7(2):222-7. [PubMed: 11175854]  [MGI Ref ID J:126862]

Rajapurohitam V; Chalhoub N; Benachenhou N; Neff L; Baron R; Vacher J. 2001. The mouse osteopetrotic grey-lethal mutation induces a defect in osteoclast maturation/function. Bone 28(5):513-23. [PubMed: 11344051]  [MGI Ref ID J:82886]

Scheppke L; Aguilar E; Gariano RF; Jacobson R; Hood J; Doukas J; Cao J; Noronha G; Yee S; Weis S; Martin MB; Soll R; Cheresh DA; Friedlander M. 2008. Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest 118(6):2337-46. [PubMed: 18483622]  [MGI Ref ID J:137697]

Schwartzberg PL; Xing L; Hoffmann O; Lowell CA; Garrett L; Boyce BF; Varmus HE. 1997. Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src-/- mutant mice. Genes Dev 11(21):2835-44. [PubMed: 9353253]  [MGI Ref ID J:44089]

Shimizu A; Maruyama T; Tamaki K; Uchida H; Asada H; Yoshimura Y. 2005. Impairment of decidualization in SRC-deficient mice. Biol Reprod 73(6):1219-27. [PubMed: 16107610]  [MGI Ref ID J:104318]

Smith CL; Mittaud P; Prescott ED; Fuhrer C; Burden SJ. 2001. Src, Fyn, and Yes are not required for neuromuscular synapse formation but are necessary for stabilization of agrin-induced clusters of acetylcholine receptors. J Neurosci 21(9):3151-60. [PubMed: 11312300]  [MGI Ref ID J:70507]

Sperber BR; Boyle-Walsh EA; Engleka MJ; Gadue P; Peterson AC; Stein PL; Scherer SS; McMorris FA. 2001. A unique role for Fyn in CNS myelination. J Neurosci 21(6):2039-47. [PubMed: 11245687]  [MGI Ref ID J:109485]

Stein PL; Vogel H; Soriano P. 1994. Combined deficiencies of Src, Fyn, and Yes tyrosine kinases in mutant mice. Genes Dev 8(17):1999-2007. [PubMed: 7958873]  [MGI Ref ID J:20346]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Thomas SM; Soriano P; Imamoto A. 1995. Specific and redundant roles of Src and Fyn in organizing the cytoskeleton. Nature 376(6537):267-71. [PubMed: 7617039]  [MGI Ref ID J:113005]

Tiffee JC; Xing L; Nilsson S; Boyce BF. 1999. Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice. Calcif Tissue Int 65(1):53-8. [PubMed: 10369734]  [MGI Ref ID J:56180]

Watkin H; Richert MM; Lewis A; Terrell K; McManaman JP; Anderson SM. 2008. Lactation failure in Src knockout mice is due to impaired secretory activation. BMC Dev Biol 8:6. [PubMed: 18215306]  [MGI Ref ID J:135235]

Xing L; Venegas AM; Chen A; Garrett-Beal L; Boyce BF; Varmus HE; Schwartzberg PL. 2001. Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival. Genes Dev 15(2):241-53. [PubMed: 11157779]  [MGI Ref ID J:67400]

Yip YP; Kronstadt-O'Brien P; Capriotti C; Cooper JA; Yip JW. 2007. Migration of sympathetic preganglionic neurons in the spinal cord is regulated by Reelin-dependent Dab1 tyrosine phosphorylation and CrkL. J Comp Neurol 502(4):635-43. [PubMed: 17394141]  [MGI Ref ID J:132843]

Zhang Q; Guo R; Lu Y; Zhao L; Zhou Q; Schwarz EM; Huang J; Chen D; Jin ZG; Boyce BF; Xing L. 2008. VEGF-C, a lymphatic growth factor, is a RANKL target gene in osteoclasts that enhances osteoclastic bone resorption through an autocrine mechanism. J Biol Chem 283(19):13491-9. [PubMed: 18359770]  [MGI Ref ID J:137099]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryThis strain was generated on an inbred 129/Sv background. The B6,129 strain is maintained by mating heterozygous siblings. Expected coat color from breeding:Black, White Bellied Agouti
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Additional Supply Details

Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryorecovery - Standard.
    The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845.

  • This strain is included in the Induced Mutant Resource Colony collection.

Control Information

  Control
   Wild-type from the colony
   101045 B6129SF2/J (approximate)
   Wildtype mice from the colony or B6129SF2 mice (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6;129 mixed background.
 
  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.

General Terms and Conditions


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