Overview

This targeted mutation of the myelocytomatosis oncogene (Myc) gene may be useful in generating conditional mutations to study B cell activation and proliferation, neural crest cell development, and mouse embryonic fibroblast proliferation.

Donating Investigator

Ignacio Moreno de Alboran, Universidad de Autonoma de Madrid

Genetic overview

Genetic Background	Generation

Myc^tm2Fwa

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Myc	myelocytomatosis oncogene

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Research Tools
Developmental Biology Research

View All Research Applications

Details

Detailed Description

Homozygote: Mice homozygous for the targeted mutation are viable and fertile and exhibit no overt phenotypic abnormalities. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific conditional mutants of the floxed gene.

Heterozygote: Not evaluated

For example, when bred to mice carrying Cd19^tm1(cre)Cgn, which expresses Cre recombinase in B lymphoctye development, this mutant mouse strain may be useful in studies of B cell proliferation and activation.

When bred to mice carrying Tg(Wnt1-cre)11Rth, which expresses Cre recombinase in the neural tube, this mutant mouse strain may be useful in studies of craniofacial development.

Development

A targeting vector was designed to place a loxP site between exons 1 and 2 and a loxP-flanked PGKneo cassette downstream of exon 3. The construct was electroporated into 129S6/SvEvTac-derived TC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The neomycin cassette was removed by transient transfection with a Cre recombinase expressing plasmid leaving loxP sites flanking exons 2 and 3. The resulting chimeric animals were crossed to C57BL/6 mice. The mice were then bred to mice on a mixed B6;129 background carrying the Mycn^tm1Psk allele. The Mycn allele was subsequently bred out of the line. The mice were then backcrossed to C57BL/6J for 6 generations before being transferred to the Repository. The mice were crossed to C57BL/6J to establish the colony.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

de Alboran IM; O'Hagan RC; Gartner F; Malynn B; Davidson L; Rickert R; Rajewsky K; DePinho RA; Alt FW. 2001. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14(1):45-55PubMed: 11163229 MGI: J:67222

View All References

Genetics

Myc^tm2Fwa

Allele Symbol: Myc^tm2Fwa

Allele Name	targeted mutation 2, Frederick W Alt
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	c-myc^fl; MYC^fl; Myc^flox; Myclox
Gene Symbol and Name	Myc, myelocytomatosis oncogene
Gene Synonym(s)
Strain of Origin	129S6/SvEvTac
Chromosome	15
Molecular Note	A single loxP site was inserted into intron 1 and a loxP-flanked neomycin selection cassette was inserted 3' to exon 3. The neomycin cassette was removed in ES cells by transient Cre expression prior to the production of chimeric mice.
Mutations Made By	Dr. Frederick Alt, Children's Hospital

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Immunology, Inflammation and Autoimmunity Research
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
Developmental Biology Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Myc^tm2Fwa/Myc^tm2Fwa
involves: 129S6/SvEvTac

normal phenotype

no abnormal phenotype detected
- Normal - homozygotes are fertile and show no obvious abnormalities

Genotype: Gt(ROSA)26Sor^tm1Sor/? Myc^tm2Fwa/Myc^tm2Fwa H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA

skeleton phenotype

short nasal bone

abnormal coronal suture morphology
- the coronal suture adjacent to the frontal bone has a curvilinear appearance and fails to fuse at the midline

abnormal malleus morphology
- Normal - however, the incus and stapes are morphologically normal
- at 6 weeks, malleal defects are observed

small malleus
- at 6 weeks, the body of the malleus is smaller than normal

small malleus manubrium
- at 6 weeks, the manubrium is smaller than normal

abnormal frontal bone morphology
- at 6 weeks, the frontal bone is defective and mostly composed of a cartilaginous membrane

craniofacial phenotype

abnormal malleus morphology
- at 6 weeks, malleal defects are observed
- Normal - however, the incus and stapes are morphologically normal

abnormal coronal suture morphology
- the coronal suture adjacent to the frontal bone has a curvilinear appearance and fails to fuse at the midline

small malleus
- at 6 weeks, the body of the malleus is smaller than normal

abnormal frontal bone morphology
- at 6 weeks, the frontal bone is defective and mostly composed of a cartilaginous membrane

short nasal bone

small malleus manubrium
- at 6 weeks, the manubrium is smaller than normal

hearing/vestibular/ear phenotype

abnormal malleus morphology
- at 6 weeks, malleal defects are observed
- Normal - however, the incus and stapes are morphologically normal

small malleus
- at 6 weeks, the body of the malleus is smaller than normal

small malleus manubrium
- at 6 weeks, the manubrium is smaller than normal

Genotype: Myc^tm2Fwa/Myc^tm2Fwa H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

absent pinna reflex
- mutant mice do not appear startled in response to a loud noise e.g. clapping of hands

growth/size/body region phenotype

decreased body weight
- mutant mice show a ~25% reduction in weight relative to control littermates

short snout
- mutant mice exhibit a persistently shorter snout

decreased body size
- mutant mice are viable but show a ~25% reduction in overall size relative to control littermates

hearing/vestibular/ear phenotype

abnormal auditory brainstem response
- mutant mice display delayed evoked response latencies

abnormal malleus morphology
- the body of malleus is abnormally shaped
- the angle between the manubrium and the body of the malleus is increased

conductive hearing impairment
- mutant mice show a significant hearing deficit attributed to malleal defects

abnormal middle ear ossicle morphology
- Normal - in addition, normal hair cells are seen in the organ of Corti, utricle, and crista, and no absence of inner or outer hair cell stereocilia is observed
- mutant mice display predominantly malleal defects
- Normal - in contrast, the structure and size of incus and stapes appears normal

short malleus manubrium
- the manubrium is shorter than normal

small malleus
- the body of malleus is smaller than normal

craniofacial phenotype

abnormal frontal bone morphology
- frontal bones are defective, with absence of ossification near the metopic region

abnormal middle ear ossicle morphology
- Normal - in addition, normal hair cells are seen in the organ of Corti, utricle, and crista, and no absence of inner or outer hair cell stereocilia is observed
- Normal - in contrast, the structure and size of incus and stapes appears normal
- mutant mice display predominantly malleal defects

small nasal bone

abnormal malleus morphology
- the body of malleus is abnormally shaped
- the angle between the manubrium and the body of the malleus is increased

short nasal bone

small cranium
- mutant mice exhibit a noticeably smaller skull

short snout
- mutant mice exhibit a persistently shorter snout

abnormal parietal bone morphology
- the relative size and position of parietal bones is abnormal

short malleus manubrium
- the manubrium is shorter than normal

small malleus
- the body of malleus is smaller than normal

integument phenotype

variable body spotting
- all mutants show coat pigmentation defects involving multiple white patches of various sizes that spare the head
- Normal - however, no other neural crest-related defects such as cleft palate, spina bifida or exencephaly are observed

pigmentation phenotype

variable body spotting
- Normal - however, no other neural crest-related defects such as cleft palate, spina bifida or exencephaly are observed
- all mutants show coat pigmentation defects involving multiple white patches of various sizes that spare the head

skeleton phenotype

abnormal malleus morphology
- the body of malleus is abnormally shaped
- the angle between the manubrium and the body of the malleus is increased

abnormal parietal bone morphology
- the relative size and position of parietal bones is abnormal

abnormal frontal bone morphology
- frontal bones are defective, with absence of ossification near the metopic region

short malleus manubrium
- the manubrium is shorter than normal

short nasal bone

abnormal middle ear ossicle morphology
- Normal - in addition, normal hair cells are seen in the organ of Corti, utricle, and crista, and no absence of inner or outer hair cell stereocilia is observed
- Normal - in contrast, the structure and size of incus and stapes appears normal
- mutant mice display predominantly malleal defects

small malleus
- the body of malleus is smaller than normal

small nasal bone

small cranium
- mutant mice exhibit a noticeably smaller skull

Genotype: Myc^tm2Fwa/Myc^tm2Fwa Cd19^tm1(cre)Cgn/Cd19⁺
involves: 129P2/OlaHsd * 129S6/SvEvTac

cellular phenotype

decreased B cell proliferation
- impaired proliferation response to stimulation; cells do not undergo activation

hematopoietic system phenotype

decreased B cell proliferation
- impaired proliferation response to stimulation; cells do not undergo activation

immune system phenotype

decreased B cell proliferation
- impaired proliferation response to stimulation; cells do not undergo activation

Genotype: Myc^tm2Fwa/Myc⁺ H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

integument phenotype

belly spot
- mutant mice display a clearly demarcated white belly spot

pigmentation phenotype

belly spot
- mutant mice display a clearly demarcated white belly spot

References

de Alboran IM; O'Hagan RC; Gartner F; Malynn B; Davidson L; Rickert R; Rajewsky K; DePinho RA; Alt FW. 2001. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14(1):45-55PubMed: 11163229 MGI: J:67222

Additional - Myc^tm2Fwa related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Myc
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S6-Myc^tm2Fwa/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32046 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

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

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Myctm2Fwa

Allele Symbol: Myctm2Fwa

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Myctm2Fwa/Myctm2Fwainvolves: 129S6/SvEvTac

normal phenotype

Genotype: Gt(ROSA)26Sortm1Sor/? Myctm2Fwa/Myctm2Fwa H2az2Tg(Wnt1-cre)11Rth/0involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA

skeleton phenotype

craniofacial phenotype

hearing/vestibular/ear phenotype

Genotype: Myctm2Fwa/Myctm2Fwa H2az2Tg(Wnt1-cre)11Rth/0involves: 129S6/SvEvTac * C57BL/6 * CBA

behavior/neurological phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

craniofacial phenotype

integument phenotype

pigmentation phenotype

skeleton phenotype

Genotype: Myctm2Fwa/Myctm2Fwa Cd19tm1(cre)Cgn/Cd19+involves: 129P2/OlaHsd * 129S6/SvEvTac

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Myctm2Fwa/Myc+ H2az2Tg(Wnt1-cre)11Rth/0involves: 129S6/SvEvTac * C57BL/6 * CBA

integument phenotype

pigmentation phenotype

References

Additional - Myctm2Fwa related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Myc^tm2Fwa

Allele Symbol: Myc^tm2Fwa

Genotype: Myc^tm2Fwa/Myc^tm2Fwa
involves: 129S6/SvEvTac

Genotype: Gt(ROSA)26Sor^tm1Sor/? Myc^tm2Fwa/Myc^tm2Fwa H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * CBA

Genotype: Myc^tm2Fwa/Myc^tm2Fwa H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

Genotype: Myc^tm2Fwa/Myc^tm2Fwa Cd19^tm1(cre)Cgn/Cd19⁺
involves: 129P2/OlaHsd * 129S6/SvEvTac

Genotype: Myc^tm2Fwa/Myc⁺ H2az2^{Tg(Wnt1-cre)11Rth}/0
involves: 129S6/SvEvTac * C57BL/6 * CBA

Additional - Myc^tm2Fwa related