Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6.129-Fmr1tm1(I304N)Rbd/J    (Changed: 23-APR-10 ) Type Congenic; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Dr. Robert B Darnell,   Rockefeller University, HHMI

Description
These mice recapitulate the phenotype of null allele mice in terms of increased macroorchidism with age, protein synthesis-dependent metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) at CA1 hippocampal neurons, and performance in multiple behavioral assays. There is a significant incidence of audiogenic seizures in adulthood. Their mRNA is of correct size and is expressed at correct levels, but protein levels are decreased to 15-30% that of wildtype, most pronounced at postnatal day 14 (P14) and normalizing somewhat in adulthood. This strain may be useful in studies of Fragile X Mental Retardation Syndrome.

Development
PCR mutagenesis was used to create an I304N mutation in exon 10, changing sequence CTG(Leu) ATT(Ile) CAA(Gln) to CTT(Leu) AAC(Asn) CAG(Gln). A loxP-Auto-Cre-NeoR-loxP (ACNF) cassette was inserted in intron 10. The targeting vector was introduced to 129-derived embryonic stem (ES) cells. The loxP-flanked segment was self-excised. This strain was backcrossed to C57BL/6 for 10 generations.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Fmr1^tm1Rbd allele

008909

FVB.129-Fmr1tm1Rbd/J

View Strains carrying   Fmr1^tm1Rbd     (1 strain)

Strains carrying other alleles of Fmr1

003025	B6.129P2-Fmr1tm1Cgr/J
003024	FVB.129P2(B6)-Fmr1tm1Cgr/J
004624	FVB.129P2-Pde6b+ Tyrc-ch Fmr1tm1Cgr/J
002700	FVB;129P-Fmr1tm1Cgr/J

View Strains carrying other alleles of Fmr1     (4 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Fragile X Mental Retardation Syndrome

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Fragile X Tremor/Ataxia Syndrome; FXTAS   (FMR1) Premature Ovarian Failure 1; POF1   (FMR1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Fmr1^tm1Rbd/Y

        B6.129-Fmr1^tm1Rbd

• behavior/neurological phenotype
• audiogenic seizures
  • increased audiogenic seizure susceptibility   (MGI Ref ID J:155593)
  • 18% of the 2-3 month old mice have audiogenic seizures, versus none in wild-type littermates   (MGI Ref ID J:155593)
• decreased anxiety-related response
  • travel a greater proportion in the center of the open field   (MGI Ref ID J:155593)
  • a greater number of light-dark transitions than their wild type littermates   (MGI Ref ID J:155593)
  • no significant difference for the total time spent in the dark   (MGI Ref ID J:155593)
• decreased startle reflex
  • lower acoustic startle compared to their wild type littermates   (MGI Ref ID J:155593)
  • no significant difference in prepulse inhibition (PPI) responses   (MGI Ref ID J:155593)
• hyperactivity
  • increased locomotor activity   (MGI Ref ID J:155593)
  • travel a greater total distance in the open field compared with their wild type littermates   (MGI Ref ID J:155593)
• increased exploration in new environment
  • increased exploratory behavior   (MGI Ref ID J:155593)
  • travel a greater total distance in the open field compared with their wild type littermates   (MGI Ref ID J:155593)
• increased stereotypic behavior
  • increased repetitive/perseverative responses   (MGI Ref ID J:155593)
  • bury significantly more marbles than their wild type littermates   (MGI Ref ID J:155593)
• increased thermal nociceptive threshold
  • greater latency to hindlimb response in hotplate than wild type mice (p=0.076)   (MGI Ref ID J:155593)
• nervous system phenotype
• abnormal long term depression
  • metabotropic glutamate receptor-dependent long term depression (mGluR-LTD) in hippocampal CA1 neurons is enhanced in the presence of anisomycin   (MGI Ref ID J:155593)
• audiogenic seizures
  • increased audiogenic seizure susceptibility   (MGI Ref ID J:155593)
  • 18% of the 2-3 month old mice have audiogenic seizures, versus none in wild-type littermates   (MGI Ref ID J:155593)
• integument phenotype
• increased thermal nociceptive threshold
  • greater latency to hindlimb response in hotplate than wild type mice (p=0.076)   (MGI Ref ID J:155593)

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Fmr1^tm1Rbd/Y

        FVB.129-Fmr1^tm1Rbd

• endocrine/exocrine gland phenotype
• increased testis weight
  • increased testis weight (12-28%)   (MGI Ref ID J:155593)
  • the most pronounced differences are evident in older animals (>5months)   (MGI Ref ID J:155593)
  • no significant difference in body weights   (MGI Ref ID J:155593)
• reproductive system phenotype
• increased testis weight
  • increased testis weight (12-28%)   (MGI Ref ID J:155593)
  • the most pronounced differences are evident in older animals (>5months)   (MGI Ref ID J:155593)
  • no significant difference in body weights   (MGI Ref ID J:155593)

View Research Applications

Research Applications

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

Neurobiology Research
Behavioral and Learning Defects
Epilepsy
Fragile X Mental Retardation Syndrome

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Fmr1tm1Rbd
Allele Name		targeted mutation 1, Robert B Darnell
Allele Type		Targeted (knock-in)
Common Name(s)		Fmr1I304N; Fmr1tm1(I304N)Drnl; Fmr1tm1(I304N)Rbd;
Mutation Made By		Dr. Robert Darnell,   Rockefeller University, HHMI
Strain of Origin		129
Promoter		Fmr1, fragile X mental retardation syndrome 1, mouse, laboratory
Molecular Note		PCR mutagenesis was used to create an I304N mutation in exon 10, changing sequence CTG(Leu) ATT(Ile) CAA(Gln) to CTT(Leu) AAC(Asn) CAG(Gln). A loxP-Auto-Cre-NeoR-loxP (ACNF) cassette was inserted in intron 10. Northern blot and quantitative RT-PCR analysis showed that the mutant mRNA was expressed at wild type level and was of the expected size in both brain and testes, but Western blot showed that protein levels were decreased to 13-30% that of wild type. Sequencing of RT-PCR products confirmed the presence of the mutation. [MGI Ref ID J:155593]

Genotyping

Genotyping Information

Genotyping Protocols

Fmr1^tm1Rbd, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Zang JB; Nosyreva ED; Spencer CM; Volk LJ; Musunuru K; Zhong R; Stone EF; Yuva-Paylor LA; Huber KM; Paylor R; Darnell JC; Darnell RB. 2009. A mouse model of the human Fragile X syndrome I304N mutation. PLoS Genet 5(12):e1000758. [PubMed: 20011099]  [MGI Ref ID J:155593]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes may be bred.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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See Terms of Use tab for General Terms and Conditions

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.

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