Overview

Also Known As:src-

These Src knock-out mice exhibit a deficiency in bone remodeling, indicating impaired osteoclast function, and developed osteopetrosis. They are suitable for use in applications related to the study of the physiological role of the Rous sarcoma oncogene.

Donating Investigator

Dr. Philippe Soriano, Mount Sinai School of Medicine

Genetic overview

Genetic Background	Generation

Src^tm1Sor

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Src	Rous sarcoma oncogene

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Research Applications

Developmental Biology Research
Cancer Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Src^tm1Sor 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 Src^tm1Sor mutation have no apparent abnormalities.

Control Suggestions

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.
Wild-type from the colony

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

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):693-702PubMed: 1997203 MGI: J:67040

View All References

Genetics

Src^tm1Sor

Allele Symbol: Src^tm1Sor

Allele Name	targeted mutation 1, Philippe Soriano
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	src^-
Gene Symbol and Name	Src, Rous sarcoma oncogene
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	2
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.
Mutations Made By	Dr. Philippe Soriano, Mount Sinai School of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Skeletal Defects
  - osteopetrosis
Internal/Organ Research
- Skeleton
  - Bone

Genotype: Src^tm1Sor related

Cancer Research
- Genes Regulating Growth and Proliferation
- Oncogenes
Developmental Biology Research
- Skeletal Defects
  - osteopetrosis

Mammalian Phenotype Terms by Genotype

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

Genotype: Src^tm1Sor/Src^tm1Sor
B6.129S7-Src/J

embryo phenotype

abnormal decidualization
- in vitro, endometrial stromal cells (ESCs) from wild-type mice became morphologically decidualized when cultured in the presence of E2+P4 for 5 days, whereas ESCs from female homozygotes remained morphologically unchanged
- ovariectomized female homozygotes treated with a low dose of estrogen (E2) and a high dose of progesterone (P4), followed by mechanical stimulation of the left uterine horn, showed little or no detectable decidual responses relative to similarly-treated wild-type and heterozygous females, as determined by uterine histology and uterine weight changes
- however, prolonged treatment with E2+P4 for 10 days elicited both functional and morphological decidualization even in homozygous mutant ESCs
- ild-type and heterozygous females, as determined by uterine histology and uterine weight changes

reproductive system phenotype

abnormal decidualization
- however, prolonged treatment with E2+P4 for 10 days elicited both functional and morphological decidualization even in homozygous mutant ESCs
- ild-type and heterozygous females, as determined by uterine histology and uterine weight changes
- ovariectomized female homozygotes treated with a low dose of estrogen (E2) and a high dose of progesterone (P4), followed by mechanical stimulation of the left uterine horn, showed little or no detectable decidual responses relative to similarly-treated wild-type and heterozygous females, as determined by uterine histology and uterine weight changes
- in vitro, endometrial stromal cells (ESCs) from wild-type mice became morphologically decidualized when cultured in the presence of E2+P4 for 5 days, whereas ESCs from female homozygotes remained morphologically unchanged

female infertility
- female homozygotes are severely subfertile or infertile, partly due to impaired decidualization resulting from the loss of maternal function in endometrial stromal cells

The following phenotype relates to a compound genotype created using this strain

Genotype: Src^tm1Sor/Src^tm1Sor
either: 129S7/SvEvBrd-Src or (involves: 129S7/SvEvBrd * C57BL/6J)

growth/size/body region phenotype

absent incisors
- incisors are absent at 3 weeks of age
- incisor teeth are well developed, but fail to erupt through the gum

abnormal tooth eruption
- some molar teeth show partial eruption, but are crowded by osseous growth of the facial bones

broad face
- mice have a broad face

abnormal head shape
- mice have a slightly domed head

decreased body size
- by 10-12 days of age, mice are noticeably smaller than controls

decreased body weight
- mice grow more slowly and weigh about one-third to one-half as much as controls

failure of tooth eruption
- incisor teeth are well developed, but fail to erupt through the gum

immune system phenotype

periodontium inflammation
- suppurative periodontal inflammation is seen in some animals

increased inflammatory response
- necrotic debris and acute inflammatory cells are sometimes seen within the lumen of the nasolacrimal duct

integument phenotype

diluted coat color
- Background Sensitivity - mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background

craniofacial phenotype

abnormal craniofacial bone morphology
- smaller airway lumina are present due to abnormal facial bone morphology
- facial bones are thickened by fibrous and osseous tissue proliferation and lack of bone resorbtion

abnormal tooth eruption
- some molar teeth show partial eruption, but are crowded by osseous growth of the facial bones

absent incisors
- incisor teeth are well developed, but fail to erupt through the gum
- incisors are absent at 3 weeks of age

abnormal head shape
- mice have a slightly domed head

broad face
- mice have a broad face

failure of tooth eruption
- incisor teeth are well developed, but fail to erupt through the gum

limbs/digits/tail phenotype

abnormal limb morphology
- enlarged, club-shaped extremities

mammalian phenotype

hematopoietic system phenotype
- Normal - normal red and white cell parameters are seen
- Normal - no evidence of hemorrhage or platelet dysfunction is seen; mice are capable of wound healing following tail or toe clipping
- Normal - Kuppfer cells in the liver are normal in quantity and morphology
- Normal - normal platelet counts are seen
- Normal - parafollicular cells of the thyroid are normal
- Normal - the liver and spleen are normal in size

nervous system phenotype
- Normal - no microscopic brain lesions are apparent in multiple substructures
- Normal - general brain architecture is normal and axon extension and fasciculation appear normal

mortality/aging

postnatal lethality, incomplete penetrance
- at 3 weeks of age, only 19% of the mice are homozygous, suggesting a partial prenatal and/or partial early postnatal lethality

premature death
- 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
- Background Sensitivity - mice on a mixed background survive longer than mice on the inbred 129S7/SvEvBrd genetic background

pigmentation phenotype

diluted coat color
- Background Sensitivity - mice on a mixed genetic background exhibit a lighter coat color unlike mice on an inbred 129S7/SvEvBrd genetic background

skeleton phenotype

abnormal tooth eruption
- some molar teeth show partial eruption, but are crowded by osseous growth of the facial bones

abnormal bone marrow morphology
- partial absence of bone marrow

abnormal bone structure

decreased bone resorption
- bone resorption is minimal to absent

decreased length of long bones
- long bones are shorter in length

osteopetrosis
- noted in calvarium, nasal turbinates, facial bones, mandible, tibia and femurs; obvious in long bones at P10 and in the crainial bones at birth

decreased compact bone thickness
- cortical bone is thinner and disorganized

increased trabecular bone mass
- there is a widening and extension of the trabecular bone deep into the distal metaphysis and diaphysis

abnormal craniofacial bone morphology
- 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

delayed endochondral bone ossification
- persistence of endochondrial primary spongiosa

abnormal long bone diaphysis morphology
- short diaphysis of the long bones

abnormal bone marrow cavity morphology
- the bone marrow cavity was filled with little room for hematopoietic elements

abnormal bone trabecula morphology
- the central trabeculae consist of calcified cartilage

abnormal long bone morphology

absent incisors
- incisor teeth are well developed, but fail to erupt through the gum
- incisors are absent at 3 weeks of age

failure of tooth eruption
- incisor teeth are well developed, but fail to erupt through the gum

increased long bone epiphyseal plate size
- thickened growth plates in the long bones

vision/eye phenotype

delayed eyelid opening

abnormal anterior eye segment morphology
- at later ages, the eyes are frequently cloudy due to secreted material

References

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):693-702PubMed: 1997203 MGI: 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):4485-9PubMed: 7685105 MGI: 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):1780-92PubMed: 8634424 MGI: 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):3151-60PubMed: 11312300 MGI: J:70507

Additional - Src^tm1Sor related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Srcalternate1
- Separated PCR:Srcalternate1
- Genotyping resources and troubleshooting
Breeding Considerations

This 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
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
  
  white-bellied agouti
  Related Genotype: A^w/?
Citation
When using the src- mouse strain in a publication, please cite the originating article(s) and include JAX stock #002381 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous or Wild-type for Src<tm1Sor>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:src-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Control Suggestions

Approximate Controls

Additional Information

Selected References

Srctm1Sor

Allele Symbol: Srctm1Sor

Disease Terms

Research Areas By Phenotype

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

Genotype: Srctm1Sor related

Mammalian Phenotype Terms by Genotype

Genotype: Srctm1Sor/Srctm1SorB6.129S7-Src/J

embryo phenotype

reproductive system phenotype

Genotype: Srctm1Sor/Srctm1Soreither: 129S7/SvEvBrd-Src or (involves: 129S7/SvEvBrd * C57BL/6J)

growth/size/body region phenotype

immune system phenotype

integument phenotype

craniofacial phenotype

limbs/digits/tail phenotype

mammalian phenotype

mortality/aging

pigmentation phenotype

skeleton phenotype

vision/eye phenotype

References

Additional References

Additional - Srctm1Sor related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Src^tm1Sor

Allele Symbol: Src^tm1Sor

Genotype: Src^tm1Sor related

Genotype: Src^tm1Sor/Src^tm1Sor
B6.129S7-Src/J

Genotype: Src^tm1Sor/Src^tm1Sor
either: 129S7/SvEvBrd-Src or (involves: 129S7/SvEvBrd * C57BL/6J)

Additional - Src^tm1Sor related