Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Hemizygote         (Female x Male) Species laboratory mouse Generation N11+1F14 (05-DEC-07)   Donating Investigator William Greenough,   Beckman Institute

Description
Mice that are homozygous for the targeted mutation are viable and fertile. Quantitative morphological analysis of dendritic spines of visual cortex pyramidal cells reveals mutant mice have more long dendritic spines, fewer short dendritic spines and more spines with an immature morphology than wildtype littermates. These mice were backcrossed for 11 generations onto the FVB background, are homozygous for the 129P2/OlaHsd wildtype Pde6b allele and do not suffer from blindness due to retinal degeneration. This mutant mouse strain may be useful in studies related to Fragile X Syndrome.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 5 of the targeted gene. The construct was electroporated into 129P2/OlaHsd derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.

Control Information

	Control
	004828 FVB.129P2-Pde6b+ Tyrc-ch/AntJ
		The control for this strain is STOCK# 4828, FVB.129P2-Pde6b+ Tyrc-ch/AntJ.
Considerations for Choosing Controls

Related Strains

Strains carrying   Fmr1^tm1Cgr allele

003025	B6.129P2-Fmr1tm1Cgr/J
003024	FVB.129P2(B6)-Fmr1tm1Cgr/J
002700	FVB;129P-Fmr1tm1Cgr/J

View Strains carrying   Fmr1^tm1Cgr     (3 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Fragile X Mental Retardation Syndrome - 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).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Fmr1^tm1Cgr/Fmr1^tm1Cgr

        involves: 129P2/OlaHsd * C57BL/6J

• behavior/neurological phenotype
• abnormal learning/ memory (MGI Ref ID J:19220)
• hyperactivity (MGI Ref ID J:19220)
• endocrine/exocrine gland phenotype
• enlarged testes (MGI Ref ID J:19220)
  • enlarged testes; however, both males and females were fertile
• reproductive system phenotype
• enlarged testes (MGI Ref ID J:19220)
  • enlarged testes; however, both males and females were fertile

Fmr1^tm1Cgr/Fmr1^tm1Cgr

        involves: 129P2/OlaHsd

• behavior/neurological phenotype
• abnormal eye blink conditioning behavior (MGI Ref ID J:101021)
  • the percentage of conditioned responses was reduced in the 2nd - 4th training sessions and peak amplitude and peak velocity were reduced in the 3rd and 4th training sessions
• abnormal learning/ memory (MGI Ref ID J:34449)
• increased startle reflex (MGI Ref ID J:101021)
  • in all eye blink conditioning training session the percentage and peak amplitudes of the startle responses were higher
• nervous system phenotype
• abnormal Purkinje cell morphology (MGI Ref ID J:101021)
  • the percentage of single climbing fiber innervation is increased, the length of spine heads and necks is increased, and spines are more irregular
• abnormal long term depression (MGI Ref ID J:101021)
  • induction of long term depression in Purkinje cells is significantly enhanced when stimulating parallel fibers
• endocrine/exocrine gland phenotype
• enlarged testes (MGI Ref ID J:34449)
  • progressive enlargement resulting in testes that were 34% bigger than those of wild-type by 168 to 170 days of age
  • however, both males and females were fertile
• reproductive system phenotype
• enlarged testes (MGI Ref ID J:34449)
  • progressive enlargement resulting in testes that were 34% bigger than those of wild-type by 168 to 170 days of age
  • however, both males and females were fertile
• hearing/vestibular/ear phenotype
• increased startle reflex (MGI Ref ID J:101021)
  • in all eye blink conditioning training session the percentage and peak amplitudes of the startle responses were higher

Fmr1^tm1Cgr/Y

        involves: 129P2/OlaHsd * C57BL/6 * FVB

• behavior/neurological phenotype
• audiogenic seizures (MGI Ref ID J:127792)
  • 72% of mice have a seizure in response to the test tone
• impaired passive avoidance behavior (MGI Ref ID J:127792)
  • mice exhibit reduced latency to enter box 24 hours after initiation of inhibitory avoidance test as compared to wildtype (inhibitory avoidance extinction behavior)
• nervous system phenotype
• abnormal dendrite morphology (MGI Ref ID J:127792)
  • dendritic spine density is increased in comparison to wildtype
• abnormal nerve fiber response (MGI Ref ID J:127792)
  • brief monocular deprivation results in substantial open-eye potentiation rather than the expected deprived-eye depression
• audiogenic seizures (MGI Ref ID J:127792)
  • 72% of mice have a seizure in response to the test tone
• growth/size phenotype
• increased body weight (MGI Ref ID J:127792)
  • 10% increase in body weight is observed by postnatal day 26, but is similar to wildtype by day 45
• endocrine/exocrine gland phenotype
• increased testis weight (MGI Ref ID J:127792)
  • increase in weight is only observed in adult (11-12 weeks)
• reproductive system phenotype
• increased testis weight (MGI Ref ID J:127792)
  • increase in weight is only observed in adult (11-12 weeks)

View Research Applications

Research Applications

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

Fmr1^tm1Cgr related

Developmental Biology Research
Internal/Organ Defects (multiple)

Mouse/Human Gene Homologs
fragile site mental retardation 1

Neurobiology Research
Behavioral and Learning Defects
Fragile X Mental Retardation Syndrome

Genes & Alleles

Gene & Allele Information

Allele Symbol		Fmr1tm1Cgr
Allele Name		targeted mutation 1, Ben Oostra
Allele Type		Targeted (knock-out)
Common Name(s)		FMRP KO; Fmr1 KO; FraX; fmr-tm1Cgr;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Fmr1, fragile X mental retardation syndrome 1 homolog
Chromosome		X
Gene Common Name(s)		FMRP; FRAXA; Fmr-1; MGC87458; POF; POF1;
General Note		Genbank: AF179463 and AF170530
Molecular Note		A neomycin resistance gene was inserted into exon 5. RT-PCR analysis on testis RNA derived from hemizygous male mice demonstrated that no detectable transcript was produced from this allele, and western blot analysis on extracts of testes, liver, kidneyand brain of hemizygous male mice confirmed that no stable encoded protein was made. [MGI Ref ID J:19220]

Genotyping

Genotyping Information

Genotyping Protocols

Fmr1^tm1Cgr, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

The Dutch-Belgium Fragile X Consortium: Bakker CE; Verheij C; Willemsen R; Vanderhelm R; Oerlemans F; Vermey M; Bygrave A; Hoogeveen AT; Oostra BA; Reyniers E; Deboulle K; Dhooge R; Cras P; Vanvelzen D; Nagels G; Martin JJ; Dedyn PP; Darby JK; Willems PJ. 1994. Fmr1 knockout mice: a model to study fragile x mental retardation. The Dutch-Belgium Fragile X Consortium Cell 78(1):23-33. [PubMed: 8033209]  [MGI Ref ID J:19220]

Additional References

Irwin SA; Idupulapati M; Gilbert ME; Harris JB; Chakravarti AB; Rogers EJ; Crisostomo RA; Larsen BP; Mehta A; Alcantara CJ; Patel B; Swain RA; Weiler IJ; Oostra BA; Greenough WT. 2002. Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 111(2):140-6. [PubMed: 12210340]  [MGI Ref ID J:78149]

Fmr1^tm1Cgr related

Antar LN; Li C; Zhang H; Carroll RC; Bassell GJ. 2006. Local functions for FMRP in axon growth cone motility and activity-dependent regulation of filopodia and spine synapses. Mol Cell Neurosci 32(1-2):37-48. [PubMed: 16631377]  [MGI Ref ID J:111946]

Aschrafi A; Cunningham BA; Edelman GM; Vanderklish PW. 2005. The fragile X mental retardation protein and group I metabotropic glutamate receptors regulate levels of mRNA granules in brain. Proc Natl Acad Sci U S A 102(6):2180-5. [PubMed: 15684045]  [MGI Ref ID J:96472]

Bakker CE; de Diego Otero Y; Bontekoe C; Raghoe P; Luteijn T; Hoogeveen AT; Oostra BA; Willemsen R. 2000. Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in the mouse Exp Cell Res 258(1):162-70. [PubMed: 10912798]  [MGI Ref ID J:63269]

Braun K; Segal M. 2000. FMRP involvement in formation of synapses among cultured hippocampal neurons. Cereb Cortex 10(10):1045-52. [PubMed: 11007555]  [MGI Ref ID J:102340]

Brennan FX; Albeck DS; Paylor R. 2006. Fmr1 knockout mice are impaired in a leverpress escape/avoidance task. Genes Brain Behav 5(6):467-71. [PubMed: 16923151]  [MGI Ref ID J:123642]

Bureau I; Shepherd GM; Svoboda K. 2008. Circuit and plasticity defects in the developing somatosensory cortex of FMR1 knock-out mice. J Neurosci 28(20):5178-88. [PubMed: 18480274]  [MGI Ref ID J:136321]

Centonze D; Rossi S; Mercaldo V; Napoli I; Ciotti MT; De Chiara V; Musella A; Prosperetti C; Calabresi P; Bernardi G; Bagni C. 2008. Abnormal striatal GABA transmission in the mouse model for the fragile X syndrome. Biol Psychiatry 63(10):963-73. [PubMed: 18028882]  [MGI Ref ID J:139619]

Chen L; Toth M. 2001. Fragile X mice develop sensory hyperreactivity to auditory stimuli. Neuroscience 103(4):1043-50. [PubMed: 11301211]  [MGI Ref ID J:85912]

Chuang SC; Zhao W; Bauchwitz R; Yan Q; Bianchi R; Wong RK. 2005. Prolonged epileptiform discharges induced by altered group I metabotropic glutamate receptor-mediated synaptic responses in hippocampal slices of a fragile X mouse model. J Neurosci 25(35):8048-55. [PubMed: 16135762]  [MGI Ref ID J:100474]

Comery TA; Harris JB; Willems PJ; Oostra BA; Irwin SA; Weiler IJ; Greenough WT. 1997. Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits. Proc Natl Acad Sci U S A 94(10):5401-4. [PubMed: 9144249]  [MGI Ref ID J:70399]

D'Antuono M; Merlo D; Avoli M. 2003. Involvement of cholinergic and gabaergic systems in the fragile X knockout mice. Neuroscience 119(1):9-13. [PubMed: 12763063]  [MGI Ref ID J:126733]

D'Hooge R; Nagels G; Franck F; Bakker CE; Reyniers E; Storm K ; Kooy RF ; Oostra BA ; Willems PJ ; De Deyn PP. 1997. Mildly impaired water maze performance in male Fmr1 knockout mice. Neuroscience 76(2):367-76. [PubMed: 9015322]  [MGI Ref ID J:38436]

D'Hulst C; De Geest N; Reeve SP; Van Dam D; De Deyn PP; Hassan BA; Kooy RF. 2006. Decreased expression of the GABA(A) receptor in fragile X syndrome. Brain Res 1121(1):238-45. [PubMed: 17046729]  [MGI Ref ID J:115258]

Desai NS; Casimiro TM; Gruber SM; Vanderklish PW. 2006. Early postnatal plasticity in neocortex of Fmr1 knockout mice. J Neurophysiol 96(4):1734-45. [PubMed: 16823030]  [MGI Ref ID J:135706]

Dictenberg JB; Swanger SA; Antar LN; Singer RH; Bassell GJ. 2008. A direct role for FMRP in activity-dependent dendritic mRNA transport links filopodial-spine morphogenesis to fragile X syndrome. Dev Cell 14(6):926-39. [PubMed: 18539120]  [MGI Ref ID J:137197]

Dobkin C; Rabe A; Dumas R; El Idrissi A; Haubenstock H; Brown WT. 2000. Fmr1 knockout mouse has a distinctive strain-specific learning impairment. Neuroscience 100(2):423-9. [PubMed: 11008180]  [MGI Ref ID J:119166]

Dolen G; Osterweil E; Rao BS; Smith GB; Auerbach BD; Chattarji S; Bear MF. 2007. Correction of Fragile X Syndrome in Mice. Neuron 56(6):955-962. [PubMed: 18093519]  [MGI Ref ID J:127792]

El Idrissi A; Ding XH; Scalia J; Trenkner E; Brown WT; Dobkin C. 2005. Decreased GABA(A) receptor expression in the seizure-prone fragile X mouse. Neurosci Lett 377(3):141-6. [PubMed: 15755515]  [MGI Ref ID J:104931]

Fisch GS; Hao HK; Bakker C; Oostra BA. 1999. Learning and memory in the FMR1 knockout mouse. Am J Med Genet 84(3):277-82. [PubMed: 10331607]  [MGI Ref ID J:54509]

Galvez R; Gopal AR; Greenough WT. 2003. Somatosensory cortical barrel dendritic abnormalities in a mouse model of the fragile X mental retardation syndrome. Brain Res 971(1):83-9. [PubMed: 12691840]  [MGI Ref ID J:83158]

Galvez R; Smith RL; Greenough WT. 2005. Olfactory bulb mitral cell dendritic pruning abnormalities in a mouse model of the Fragile-X mental retardation syndrome: further support for FMRP's involvement in dendritic development. Brain Res Dev Brain Res 157(2):214-6. [PubMed: 15878626]  [MGI Ref ID J:104546]

Gantois I; Vandesompele J; Speleman F; Reyniers E; D'Hooge R; Severijnen LA; Willemsen R; Tassone F; Kooy RF. 2006. Expression profiling suggests underexpression of the GABA(A) receptor subunit delta in the fragile X knockout mouse model Neurobiol Dis 21:346-357. [PubMed: 16199166]  [MGI Ref ID J:105740]

Giuffrida R; Musumeci S; D'Antoni S; Bonaccorso CM; Giuffrida-Stella AM; Oostra BA; Catania MV. 2005. A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome. J Neurosci 25(39):8908-16. [PubMed: 16192381]  [MGI Ref ID J:101346]

Godfraind JM; Reyniers E; De Boulle K; D'Hooge R; De Deyn PP; Bakker CE; Oostra BA; Kooy RF; Willems PJ. 1996. Long-term potentiation in the hippocampus of fragile X knockout mice. Am J Med Genet 64(2):246-51. [PubMed: 8844057]  [MGI Ref ID J:34552]

Grossman AW; Elisseou NM; McKinney BC; Greenough WT. 2006. Hippocampal pyramidal cells in adult Fmr1 knockout mice exhibit an immature-appearing profile of dendritic spines. Brain Res 1084(1):158-164. [PubMed: 16574084]  [MGI Ref ID J:108977]

Gruss M; Braun K. 2004. Age- and region-specific imbalances of basal amino acids and monoamine metabolism in limbic regions of female Fmr1 knock-out mice. Neurochem Int 45(1):81-8. [PubMed: 15082225]  [MGI Ref ID J:101787]

Hayashi ML; Rao BS; Seo JS; Choi HS; Dolan BM; Choi SY; Chattarji S; Tonegawa S. 2007. Inhibition of p21-activated kinase rescues symptoms of fragile X syndrome in mice. Proc Natl Acad Sci U S A 104(27):11489-11494. [PubMed: 17592139]  [MGI Ref ID J:122818]

Hou L; Antion MD; Hu D; Spencer CM; Paylor R; Klann E. 2006. Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression. Neuron 51(4):441-54. [PubMed: 16908410]  [MGI Ref ID J:122974]

Hu H; Qin Y; Bochorishvili G; Zhu Y; van Aelst L; Zhu JJ. 2008. Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. J Neurosci 28(31):7847-62. [PubMed: 18667617]  [MGI Ref ID J:139516]

Huber KM; Gallagher SM; Warren ST; Bear MF. 2002. Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99(11):7746-50. [PubMed: 12032354]  [MGI Ref ID J:76865]

Irwin SA; Idupulapati M; Gilbert ME; Harris JB; Chakravarti AB; Rogers EJ; Crisostomo RA; Larsen BP; Mehta A; Alcantara CJ; Patel B; Swain RA; Weiler IJ; Oostra BA; Greenough WT. 2002. Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice. Am J Med Genet 111(2):140-6. [PubMed: 12210340]  [MGI Ref ID J:78149]

Ivanco TL; Greenough WT. 2002. Altered mossy fiber distributions in adult Fmr1 (FVB) knockout mice. Hippocampus 12(1):47-54. [PubMed: 11918288]  [MGI Ref ID J:113177]

Kim SH; Markham JA; Weiler IJ; Greenough WT. 2008. Aberrant early-phase ERK inactivation impedes neuronal function in fragile X syndrome. Proc Natl Acad Sci U S A 105(11):4429-34. [PubMed: 18332424]  [MGI Ref ID J:133336]

Koekkoek SK; Yamaguchi K; Milojkovic BA; Dortland BR; Ruigrok TJ; Maex R; De Graaf W; Smit AE; VanderWerf F; Bakker CE; Willemsen R; Ikeda T; Kakizawa S; Onodera K; Nelson DL; Mientjes E; Joosten M; De Schutter E; Oostra BA; Ito M; De Zeeuw CI. 2005. Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron 47(3):339-52. [PubMed: 16055059]  [MGI Ref ID J:101021]

Kooy RF; D'Hooge R; Reyniers E; Bakker CE; Nagels G; De Boulle K; Storm K; Clincke G; De Deyn PP; Oostra BA; Willems PJ. 1996. Transgenic mouse model for the fragile X syndrome. Am J Med Genet 64(2):241-5. [PubMed: 8844056]  [MGI Ref ID J:34449]

Kooy RF; Reyniers E; Verhoye M; Sijbers J; Bakker CE; Oostra BA; Willems PJ; Van Der Linden A. 1999. Neuroanatomy of the fragile X knockout mouse brain studied using in vivo high resolution magnetic resonance imaging. Eur J Hum Genet 7(5):526-32. [PubMed: 10439957]  [MGI Ref ID J:103315]

Larson J; Jessen RE; Kim D; Fine AK; du Hoffmann J. 2005. Age-dependent and selective impairment of long-term potentiation in the anterior piriform cortex of mice lacking the fragile X mental retardation protein. J Neurosci 25(41):9460-9. [PubMed: 16221856]  [MGI Ref ID J:101394]

Larson J; Kim D; Patel RC; Floreani C. 2008. Olfactory discrimination learning in mice lacking the fragile X mental retardation protein. Neurobiol Learn Mem 90(1):90-102. [PubMed: 18289890]  [MGI Ref ID J:139604]

Lauterborn JC. 2004. Stress induced changes in cortical and hypothalamic c-fos expression are altered in fragile X mutant mice. Brain Res Mol Brain Res 131(1-2):101-9. [PubMed: 15530658]  [MGI Ref ID J:109325]

Lauterborn JC; Rex CS; Kramar E; Chen LY; Pandyarajan V; Lynch G; Gall CM. 2007. Brain-derived neurotrophic factor rescues synaptic plasticity in a mouse model of fragile X syndrome. J Neurosci 27(40):10685-94. [PubMed: 17913902]  [MGI Ref ID J:125595]

Li J; Pelletier MR; Perez Velazquez JL; Carlen PL. 2002. Reduced Cortical Synaptic Plasticity and GluR1 Expression Associated with Fragile X Mental Retardation Protein Deficiency. Mol Cell Neurosci 19(2):138-51. [PubMed: 11860268]  [MGI Ref ID J:75442]

Lu R; Wang H; Liang Z; Ku L; O'donnell WT; Li W; Warren ST; Feng Y. 2004. The fragile X protein controls microtubule-associated protein 1B translation and microtubule stability in brain neuron development. Proc Natl Acad Sci U S A 101(42):15201-6. [PubMed: 15475576]  [MGI Ref ID J:93541]

Markham JA; Beckel-Mitchener AC; Estrada CM; Greenough WT. 2006. Corticosterone response to acute stress in a mouse model of Fragile X syndrome. Psychoneuroendocrinology 31(6):781-5. [PubMed: 16621323]  [MGI Ref ID J:112825]

Meredith RM; Holmgren CD; Weidum M; Burnashev N; Mansvelder HD. 2007. Increased threshold for spike-timing-dependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1. Neuron 54(4):627-38. [PubMed: 17521574]  [MGI Ref ID J:122303]

Mineur YS; Huynh LX; Crusio WE. 2006. Social behavior deficits in the Fmr1 mutant mouse. Behav Brain Res 168(1):172-5. [PubMed: 16343653]  [MGI Ref ID J:105026]

Mineur YS; Sluyter F; de Wit S; Oostra BA; Crusio WE. 2002. Behavioral and neuroanatomical characterization of the Fmr1 knockout mouse. Hippocampus 12(1):39-46. [PubMed: 11918286]  [MGI Ref ID J:113306]

Miyashiro KY; Beckel-Mitchener A; Purk TP; Becker KG; Barret T; Liu L; Carbonetto S; Weiler IJ; Greenough WT; Eberwine J. 2003. RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice. Neuron 37(3):417-31. [PubMed: 12575950]  [MGI Ref ID J:107689]

Musumeci SA; Bosco P; Calabrese G; Bakker C; De Sarro GB; Elia M; Ferri R; Oostra BA. 2000. Audiogenic seizures susceptibility in transgenic mice with fragile X syndrome. Epilepsia 41(1):19-23. [PubMed: 10643918]  [MGI Ref ID J:60043]

Nielsen DM; Derber WJ; McClellan DA; Crnic LS. 2002. Alterations in the auditory startle response in Fmr1 targeted mutant mouse models of fragile X syndrome. Brain Res 927(1):8-17. [PubMed: 11814427]  [MGI Ref ID J:74592]

Nimchinsky EA; Oberlander AM; Svoboda K. 2001. Abnormal development of dendritic spines in FMR1 knock-out mice. J Neurosci 21(14):5139-46. [PubMed: 11438589]  [MGI Ref ID J:70178]

Nosyreva ED; Huber KM. 2006. Metabotropic receptor-dependent long-term depression persists in the absence of protein synthesis in the mouse model of fragile X syndrome. J Neurophysiol 95(5):3291-5. [PubMed: 16452252]  [MGI Ref ID J:135796]

Pacey LK; Doering LC. 2007. Developmental expression of FMRP in the astrocyte lineage: implications for fragile X syndrome. Glia 55(15):1601-9. [PubMed: 17823967]  [MGI Ref ID J:127940]

Paradee W; Melikian HE; Rasmussen DL; Kenneson A; Conn PJ; Warren ST. 1999. Fragile X mouse: strain effects of knockout phenotype and evidence suggesting deficient amygdala function. Neuroscience 94(1):185-92. [PubMed: 10613508]  [MGI Ref ID J:59781]

Price TJ; Rashid MH; Millecamps M; Sanoja R; Entrena JM; Cervero F. 2007. Decreased nociceptive sensitization in mice lacking the fragile X mental retardation protein: role of mGluR1/5 and mTOR. J Neurosci 27(51):13958-67. [PubMed: 18094233]  [MGI Ref ID J:129270]

Qin M; Kang J; Burlin TV; Jiang C; Smith CB. 2005. Postadolescent changes in regional cerebral protein synthesis: an in vivo study in the FMR1 null mouse. J Neurosci 25(20):5087-95. [PubMed: 15901791]  [MGI Ref ID J:98726]

Qin M; Kang J; Smith CB. 2005. A null mutation for Fmr1 in female mice: effects on regional cerebral metabolic rate for glucose and relationship to behavior. Neuroscience 135(3):999-1009. [PubMed: 16154294]  [MGI Ref ID J:104426]

Qin M; Kang J; Smith CB. 2002. Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation. Proc Natl Acad Sci U S A 99(24):15758-63. [PubMed: 12427968]  [MGI Ref ID J:80518]

Restivo L; Ferrari F; Passino E; Sgobio C; Bock J; Oostra BA; Bagni C; Ammassari-Teule M. 2005. Enriched environment promotes behavioral and morphological recovery in a mouse model for the fragile X syndrome. Proc Natl Acad Sci U S A 102(32):11557-62. [PubMed: 16076950]  [MGI Ref ID J:100841]

Reyniers E; Van Bockstaele DR; De Boulle K; Kooy RF; Bakker CE; Oostra BA; Willems PJ. 1996. Mean corpuscular hemoglobin is not increased in Fmr1 knockout mice. Hum Genet 97(1):49-50. [PubMed: 8557260]  [MGI Ref ID J:31093]

Segal M; Kreher U; Greenberger V; Braun K. 2003. Is fragile X mental retardation protein involved in activity-induced plasticity of dendritic spines? Brain Res 972(1-2):9-15. [PubMed: 12711073]  [MGI Ref ID J:107795]

Selby L; Zhang C; Sun QQ. 2007. Major defects in neocortical GABAergic inhibitory circuits in mice lacking the fragile X mental retardation protein. Neurosci Lett 412(3):227-32. [PubMed: 17197085]  [MGI Ref ID J:119086]

Slegtenhorst-Eegdeman KE; de Rooij DG; Verhoef-Post M; van de Kant HJ; Bakker CE; Oostra BA; Grootegoed JA; Themmen AP. 1998. Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development. Endocrinology 139(1):156-62. [PubMed: 9421410]  [MGI Ref ID J:44826]

Spencer CM; Alekseyenko O; Serysheva E; Yuva-Paylor LA; Paylor R. 2005. Altered anxiety-related and social behaviors in the Fmr1 knockout mouse model of fragile X syndrome. Genes Brain Behav 4(7):420-30. [PubMed: 16176388]  [MGI Ref ID J:114353]

Spencer CM; Serysheva E; Yuva-Paylor LA; Oostra BA; Nelson DL; Paylor R. 2006. Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins. Hum Mol Genet 15(12):1984-94. [PubMed: 16675531]  [MGI Ref ID J:112066]

Steward O; Bakker CE; Willems PJ; Oostra BA. 1998. No evidence for disruption of normal patterns of mRNA localization in dendrites or dendritic transport of recently synthesized mRNA in FMR1 knockout mice, a model for human fragile-X mental retardation syndrome. Neuroreport 9(3):477-81. [PubMed: 9512393]  [MGI Ref ID J:103598]

Tervonen T; Akerman K; Oostra BA; Castren M. 2005. Rgs4 mRNA expression is decreased in the brain of Fmr1 knockout mouse. Brain Res Mol Brain Res 133(1):162-5. [PubMed: 15661377]  [MGI Ref ID J:95566]

Van Dam D; D'Hooge R; Hauben E; Reyniers E; Gantois I; Bakker CE; Oostra BA; Kooy RF; De Deyn PP. 2000. Spatial learning, contextual fear conditioning and conditioned emotional response in Fmr1 knockout mice. Behav Brain Res 117(1-2):127-36. [PubMed: 11099766]  [MGI Ref ID J:96655]

Wang H; Wu LJ; Zhang F; Zhuo M. 2008. Roles of calcium-stimulated adenylyl cyclase and calmodulin-dependent protein kinase IV in the regulation of FMRP by group I metabotropic glutamate receptors. J Neurosci 28(17):4385-97. [PubMed: 18434517]  [MGI Ref ID J:134617]

Weiler IJ; Spangler CC; Klintsova AY; Grossman AW; Kim SH; Bertaina-Anglade V; Khaliq H; de Vries FE; Lambers FA; Hatia F; Base CK; Greenough WT. 2004. Fragile X mental retardation protein is necessary for neurotransmitter-activated protein translation at synapses. Proc Natl Acad Sci U S A 101(50):17504-9. [PubMed: 15548614]  [MGI Ref ID J:94717]

Westmark CJ; Malter JS. 2007. FMRP Mediates mGluR5-Dependent Translation of Amyloid Precursor Protein. PLoS Biol 5(3):e52. [PubMed: 17298186]  [MGI Ref ID J:122019]

Wilson BM; Cox CL. 2007. Absence of metabotropic glutamate receptor-mediated plasticity in the neocortex of fragile X mice. Proc Natl Acad Sci U S A 104(7):2454-9. [PubMed: 17287348]  [MGI Ref ID J:119740]

Yan QJ; Asafo-Adjei PK; Arnold HM; Brown RE; Bauchwitz RP. 2004. A phenotypic and molecular characterization of the fmr1-tm1Cgr fragile X mouse. Genes Brain Behav 3(6):337-59. [PubMed: 15544577]  [MGI Ref ID J:104517]

Yun SW; Platholi J; Flaherty MS; Fu W; Kottmann AH; Toth M. 2006. Fmrp is required for the establishment of the startle response during the critical period of auditory development. Brain Res 1110(1):159-65. [PubMed: 16887106]  [MGI Ref ID J:113024]

Zalfa F; Eleuteri B; Dickson KS; Mercaldo V; De Rubeis S; di Penta A; Tabolacci E; Chiurazzi P; Neri G; Grant SG; Bagni C. 2007. A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 10(5):578-87. [PubMed: 17417632]  [MGI Ref ID J:121659]

Zhang J; Fang Z; Jud C; Vansteensel MJ; Kaasik K; Lee CC; Albrecht U; Tamanini F; Meijer JH; Oostra BA; Nelson DL. 2008. Fragile X-related proteins regulate mammalian circadian behavioral rhythms. Am J Hum Genet 83(1):43-52. [PubMed: 18589395]  [MGI Ref ID J:139265]

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Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	The resulting chimeric male animal was crossed to a FVB female, and then backcrossed to the FVB background for 11 generations.
Mating System	Homozygote x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	004828 FVB.129P2-Pde6b+ Tyrc-ch/AntJ
		The control for this strain is STOCK# 4828, FVB.129P2-Pde6b+ Tyrc-ch/AntJ.
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

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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.