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| Mice homozygous for this targeted allele (Nf123a-/-) lack the alternatively spliced exon 23a (which modifies the GTPase-activating protein (GAP) domain of Nf1). These mutant mice may be useful for neurological studies of Neurofibromatosis Type I, growth, differentiation, and learning and memory. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Alcino Silva, University of California, Los Angeles Description
Mice homozygous for this targeted allele (Nf123a-/-) lack the alternatively spliced exon 23a (which modifies the GTPase-activating protein (GAP) domain of Nf1), and are viable and fertile. Protein and mRNA isolated from homozygous brain tissue shows normal type I (exon 1-21 containing) neurofibromin isoform but absence of the alternatively spliced, exon 23a-containing type II neurofibromin isoform (which has a greater affinity for Ras but lower GAP activity than the type I isoform). Homozygotes have no reported increase in tumor predisposition, but show specific learning impairments in contextual discrimination, spatial learning, and coordination. These Nf123a-/- mutant mice may be useful for neurological studies of Neurofibromatosis Type I, growth, differentiation, and learning and memory.Development
A targeting vector was designed to replace 300 bp (including exon 23a) of the targeted gene with a neo cassette. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred with C57BL/6J females. These resulting Nf123a- mutant mice were then backcrossed to C57BL/6NTac for at least seven generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| 005304 C57BL/6NJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Nf1
002646 B6.129S6-Nf1tm1Fcr/J 008191 B6;129S2-Trp53tm1Tyj Nf1tm1Tyj/J View Strains carrying other alleles of Nf1 (2 strains)
Additional Web Information
Congenic Nomenclature
Phenotype
Phenotype Information
Neurofibromatosis, Type I; NF1 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Nf1tm1Cbr/Nf1+
involves: 129S1/Sv * C57BL/6
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:68489)
- mice do not have an increase in predisposition for tumor formation
Nf1tm1Cbr/Nf1tm1Cbr
involves: 129S1/Sv * C57BL/6
- behavior/neurological phenotype
- abnormal discrimination learning (MGI Ref ID J:68489)
- mice exhibit impaired contextual discrimination; during first two days of training, mutants do not discriminate between a chamber in which they receive a mild shock and a chamber in which they do not, however after 3 days of training, begin to discriminate between the chambers
- abnormal spatial learning (MGI Ref ID J:68489)
- in a probe trial, mutants search randomly rather than selectively, and spend significantly less time searching for the platform in the training quadrant than wild-type
- additional training alleviates the learning deficits
- impaired coordination (MGI Ref ID J:68489)
- mice fall off a rotating rod sooner than wild-type, however swimming speed, ambulance, exploratory behavior, and muscular strength are normal
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:68489)
- mice do not have an increase in predisposition for tumor formation
- nervous system phenotype
- *normal* nervous system phenotype (MGI Ref ID J:68489)
- mice do not exhibit gross or microscopic abnormalities in the brain, including no astrogliosis
This mouse can be used to support research in many areas including:
Mouse/Human Gene Homologs
Neurofibromatosis Type I
Neurobiology Research
Behavioral and Learning Defects
Research Tools
Neurobiology Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Nf1tm1Cbr | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Camilyn Brannan | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | Nf123a-/-; | ||
| Mutation Made By | Alcino Silva, University of California, Los Angeles | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| ES Cell Line Name | CJ7 | ||
| ES Cell Line Strain | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Nf1, neurofibromatosis 1 | ||
| Chromosome | 11 | ||
| Gene Common Name(s) | AW494271; DKFZp686J1293; FLJ21220; NFNS; Nf-1; VRNF; WSS; expressed sequence AW494271; neurofibromin; | ||
| Molecular Note | Insertion of a neomycin resistance cassette replaced 300 bp of genomic DNA including exon 23a. RT-PCR analysis of brain detected neurofibromin type I but not the type II isoform in homozygous mutant mice. Western blot analysis detected the type I but notthe type II neurofibronin in brain of homozygous mutant mice. Immunohistochemical analysis of brain did not detect type II neurofibromin isoform in homozygous mutant mice. [MGI Ref ID J:68489] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Nf1tm1Cbr, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Costa RM; Yang T; Huynh DP; Pulst SM; Viskochil DH; Silva AJ; Brannan CI. 2001. Learning deficits, but normal development and tumor predisposition, in mice lacking exon 23a of Nf1. Nat Genet 27(4):399-405. [PubMed: 11279521] [MGI Ref ID J:68489]
Additional References
Nf1tm1Cbr relatedDevon RS. 2001. Clin Genet 60:99-103. [MGI Ref ID J:71298]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date:
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | (approximate) | |
| 005304 C57BL/6NJ | (approximate) | |
| 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
See Terms of Use
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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.Ordering and Purchasing Information
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