Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation F?+G3+F1p (10-APR-05)   Donating Investigator Thomas Doetschman,   Univ of Cincinnati College of Medicine

Description
Mice homozygous for the Fgf2^tm1Doe targeted-mutant allele have low blood pressure, presumably resulting from low vascular tone, increased megakaryocyte colony stimulation activity-induced megakaryocyte colony formation; increased platelet counts, and decreased IL3-induced colony formation. Vessel layer hypertrophy following vessel injury is not altered in the absence of FGF2. Cardiac hypertrophic response to induced high blood pressure is severely blunted in the absence of FGF2. Both sexes of the mutant exhibit no discernible morphologic or behavioral defects and have a normal life span. Both sexes are fertile and fecundity is normal.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Fgf2^tm1Doe/Fgf2^tm1Doe

        involves: 129P2/OlaHsd * Black Swiss

• cardiovascular system phenotype
• decreased left ventricular developed pressure (MGI Ref ID J:45775)
  • 98.3+/-5.6 mmHg compared to 123.2+/-7.8 mmHg in wild-type mice
  • maximal rate of ventricular contraction is decreased 7011.6+/-567 mmHg/s compared to 8631.6+/-746.6 mmHg/s in wild-type mice while maximum rate of ventricular relaxation is increased -7616.5+/-499.3 mmHg/s compared to -10716+/-713.8 mmHg/s in wild-type mice
• decreased mean arterial blood pressure (MGI Ref ID J:45775)
  • 78.0+/-5.9 mmHg compared to 98.9+/-5.6 mmHg in wild-type mice
• hematopoietic system phenotype
• abnormal common myeloid progenitor cell morphology (MGI Ref ID J:45775)
  • when cultured on methylcellulose bone marrow cells generate fewer IL-3-producing colonies and increased megakaryocyte colony-stimulating activity-induced megakaryocyte colonies compared to wild-type cells
  • however, bone marrow cell culture response to granulocyte monocyte colony stimulating factor (GM-CSF) and erythropoietin, mitogen promoting granulocyte/macrophage and erythroid lineages, respectively, is normal
• increased platelet cell number (MGI Ref ID J:45775)
  • 669+/-87x10³/mm³ compared to 472+/-68x10³/mm³ in wild-type mice
  • however, platelet aggregation is normal
• muscle phenotype
• decreased vascular smooth muscle contraction (MGI Ref ID J:45775)
  • in the portal vein spontaneous contractile activity and force generated are decreased
  • however, sensitivity to phenylephrine and injury-induced vascular hyperplasia are normal
• nervous system phenotype
• abnormal neurogenesis (MGI Ref ID J:126024)
  • neurogenesis following treatment with kainic acid or middle cerebral artery occlusion (MCAO) is less than in wild-type mice at days 9 and 16 post-treatment
  • the number of proliferating cells following treatment with kainic acid is increased 2.4-fold compared to 6.8-fold in wild-type mice
  • the number of proliferating cells following MCAO is increased 1.6-fold compared to 4.2-fold in wild-type mice
  • the proportion of differentiating cells induced by kainic acid and MCAO reduced compared to in wild-type mice
  • however, mice do not display an increase seizure following kainic acid treatment or difference in blood flow, mean arterial blood pressure or infarct size following MCAO
• abnormal neuron morphology (MGI Ref ID J:126973)
  • neuron density in the surpragranular layer is decreased by 60% compared to in wild-type mice
  • mice exhibit a 45% decrease in SMI-32+ cell density in the infragranular layer with a decrease in neurophil staining of the frontal and parietal cortices
• abnormal pyramidal neuron morphology (MGI Ref ID J:126973)
  • pyramidal cell somata are smaller than in wild-type mice
  • pyramidal cell dendritic staining is decreased compared to in wild-type mice
• decreased pyramidal neuron number (MGI Ref ID J:126973)
  • the number of pyramidal neurons in the cortex is decreased in all cortical layers
  • however, the number of interneurons is unchanged
• loss of glutamate neurons (MGI Ref ID J:126973)
  • glutamate-immunoreactive cells in the dorsolateral prefrontal and parietal cortices are reduced in number
  • however, glutamate cell density in the occipital cortex is normal
  • the number of excitatory neurons (glutamate+) is decreased by 38% compared to in wild-type mice
  • fewer glutamate staining cells are found in the entire cerebral cortex compared to in wild-type mice with anterior cortical region exhibiting a more pronounced lack than the posterior region
• behavior/neurological phenotype
• abnormal sleep pattern (MGI Ref ID J:126973)
  • in 3 to 4 month old male mice treated with PTB (a GABA receptor agonist), sleep time is increased (218+/-7 minutes compared to 159+/-904 minutes for wild-type mice)
  • in 4 to 5 month old female mice treated with PTB (a GABA receptor agonist), sleep time is increased (118+/-19 minutes compared to 88+/-15 for wild-type mice)

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

Fgf2^tm1Doe/Fgf2^tm1Doe

        B6.129P2-Fgf2^tm1Doe

• cardiovascular system phenotype
• abnormal vascular endothelial cell migration (MGI Ref ID J:114567)
  • following de-endothelialization and treatment with 17beta-Estradiol (E2), mice fail to re-endothelialize the site of injury unlike wild-type mice
  • endothelial precursor cell migration in response to E2 is disrupted

Fgf2^tm1Doe/Fgf2^tm1Doe

        involves: 129P2/OlaHsd * C57BL/6

• cardiovascular system phenotype
• altered response to myocardial infarction (MGI Ref ID J:126804)
  • left ventricle chamber is increased 10-fold 4 weeks after infarct induction compared to wild-type mice in which dilation is 6-fold
  • expansion index at 4 weeks post-infarct induction is twice as much as in wild-type mice
  • following infarct induction mice exhibit less cardiomyocyte hypertrophy (4% increase in cross-section area compared to 19% increase in cross-section area in wild-type mice)
  • fibroblast proliferation at 4 days and 1 week post-infarct induction is decreased 33% and 59%, respectively, compared to in wild-type mice
  • interstitial fibrosis fails to increase as in wild-type mice after infarct induction
  • the decline in vascular density declines more dramatically following myocardial infarct induction compared to in wild-type mice (74% versus 25% at week 1 week, 91% versus 75% at 4 weeks)
  • following myocardial infarct induction, the average area per vessel is increased 10-fold compared to in wild-type mice (122.9+/-23.4 um² compared to 38.7+/-7.9 um² in wild-type mice and these large sinusoidal vessels often lack smooth muscle/pericyte investment
  • however, vessel area is unchanged even after myocardial infarct induction
  • following infarct induction, left ventricular function is decreased 20% compared to 11% in wild-type mice
• increased infarction size (MGI Ref ID J:126804)
  • cardiac infarcts fail to undergo scar contraction after 4 weeks as in wild-type mice
  • however, there is no difference in infarct composition or initial size
• homeostasis/metabolism phenotype
• altered response to myocardial infarction (MGI Ref ID J:126804)
  • left ventricle chamber is increased 10-fold 4 weeks after infarct induction compared to wild-type mice in which dilation is 6-fold
  • expansion index at 4 weeks post-infarct induction is twice as much as in wild-type mice
  • following infarct induction mice exhibit less cardiomyocyte hypertrophy (4% increase in cross-section area compared to 19% increase in cross-section area in wild-type mice)
  • fibroblast proliferation at 4 days and 1 week post-infarct induction is decreased 33% and 59%, respectively, compared to in wild-type mice
  • interstitial fibrosis fails to increase as in wild-type mice after infarct induction
  • the decline in vascular density declines more dramatically following myocardial infarct induction compared to in wild-type mice (74% versus 25% at week 1 week, 91% versus 75% at 4 weeks)
  • following myocardial infarct induction, the average area per vessel is increased 10-fold compared to in wild-type mice (122.9+/-23.4 um² compared to 38.7+/-7.9 um² in wild-type mice and these large sinusoidal vessels often lack smooth muscle/pericyte investment
  • however, vessel area is unchanged even after myocardial infarct induction
  • following infarct induction, left ventricular function is decreased 20% compared to 11% in wild-type mice
• increased infarction size (MGI Ref ID J:126804)
  • cardiac infarcts fail to undergo scar contraction after 4 weeks as in wild-type mice
  • however, there is no difference in infarct composition or initial size

View Research Applications

Research Applications

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

Fgf2^tm1Doe related

Cancer Research
Genes Regulating Growth and Proliferation

Cardiovascular Research
Hypotension
Vascular Defects

Cell Biology Research
Genes Regulating Growth and Proliferation

Hematological Research
Hematopoietic Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Fgf2tm1Doe
Allele Name		targeted mutation 1, Thomas Doetschman
Allele Type		Targeted (knock-out)
Common Name(s)		FGF-2-; Fgf2-;
Mutation Made By		Thomas Doetschman,   Univ of Cincinnati College of Medicine
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Fgf2, fibroblast growth factor 2
Chromosome		3
Gene Common Name(s)		BFGF; FGFB; Fgf-2; Fgfb; HBGF-2; fibroblast growth factor, basic;
Molecular Note		An Hprt minigene replaced 0.5kb of sequence containing 121bp of the proximal promoter region and exon 1. Northern blot analysis of E13.5 embryos demonstrated that no mRNA containing exon 2 and 3 sequences is detectable in homozygous mutant mice. Western blot analysis on brain tissue from homozygous mutant mice showed that the protein is absent. [MGI Ref ID J:45775]

Genotyping

Genotyping Information

Genotyping Protocols

Fgf2^tm1Doe, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zhou M; Sutliff RL; Paul RJ; Lorenz JN; Hoying JB; Haudenschild CC ; Yin M ; Coffin JD ; Kong L ; Kranias EG ; Luo W ; Boivin GP ; Duffy JJ ; Pawlowski SA ; Doetschman T. 1998. Fibroblast growth factor 2 control of vascular tone. Nat Med 4(2):201-7. [PubMed: 9461194]  [MGI Ref ID J:45775]

Additional References

Jungnickel J; Claus P; Gransalke K; Timmer M; Grothe C. 2004. Targeted disruption of the FGF-2 gene affects the response to peripheral nerve injury. Mol Cell Neurosci 25(3):444-52. [PubMed: 15033172]  [MGI Ref ID J:89373]

Montero A; Okada Y; Tomita M; Ito M; Tsurukami H; Nakamura T; Doetschman T; Coffin JD; Hurley MM. 2000. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest 105(8):1085-93. [PubMed: 10772653]  [MGI Ref ID J:78866]

Fgf2^tm1Doe related

Armstrong RC; Le TQ; Frost EE; Borke RC; Vana AC. 2002. Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J Neurosci 22(19):8574-85. [PubMed: 12351731]  [MGI Ref ID J:79214]

Cheng Y; Black IB; DiCicco-Bloom E. 2002. Hippocampal granule neuron production and population size are regulated by levels of bFGF. Eur J Neurosci 15(1):3-12. [PubMed: 11860501]  [MGI Ref ID J:107796]

Fadda P; Bedogni F; Fresu A; Collu M; Racagni G; Riva MA. 2007. Reduction of corticostriatal glutamatergic fibers in basic fibroblast growth factor deficient mice is associated with hyperactivity and enhanced dopaminergic transmission. Biol Psychiatry 62(3):235-42. [PubMed: 17161387]  [MGI Ref ID J:129589]

Fontaine V; Filipe C; Werner N; Gourdy P; Billon A; Garmy-Susini B; Brouchet L; Bayard F; Prats H; Doetschman T; Nickenig G; Arnal JF. 2006. Essential role of bone marrow fibroblast growth factor-2 in the effect of estradiol on reendothelialization and endothelial progenitor cell mobilization. Am J Pathol 169(5):1855-62. [PubMed: 17071606]  [MGI Ref ID J:114567]

Garmy-Susini B; Delmas E; Gourdy P; Zhou M; Bossard C; Bugler B; Bayard F; Krust A; Prats AC; Doetschman T; Prats H; Arnal JF. 2004. Role of fibroblast growth factor-2 isoforms in the effect of estradiol on endothelial cell migration and proliferation. Circ Res 94(10):1301-9. [PubMed: 15073041]  [MGI Ref ID J:94550]

Haul S; Godecke A; Schrader J; Haas HL; Luhmann HJ. 1999. Impairment of neocortical long-term potentiation in mice deficient of endothelial nitric oxide synthase. J Neurophysiol 81(2):494-7. [PubMed: 10036253]  [MGI Ref ID J:103986]

House SL; Bolte C; Zhou M; Doetschman T; Klevitsky R; Newman G; Schultz Jel J. 2003. Cardiac-specific overexpression of fibroblast growth factor-2 protects against myocardial dysfunction and infarction in a murine model of low-flow ischemia. Circulation 108(25):3140-8. [PubMed: 14656920]  [MGI Ref ID J:102944]

Hurley MM; Okada Y; Xiao L; Tanaka Y; Ito M; Okimoto N; Nakamura T; Rosen CJ; Doetschman T; Coffin JD. 2006. Impaired bone anabolic response to parathyroid hormone in Fgf2-/- and Fgf2+/- mice. Biochem Biophys Res Commun 341(4):989-94. [PubMed: 16455048]  [MGI Ref ID J:105866]

Jungnickel J; Claus P; Gransalke K; Timmer M; Grothe C. 2004. Targeted disruption of the FGF-2 gene affects the response to peripheral nerve injury. Mol Cell Neurosci 25(3):444-52. [PubMed: 15033172]  [MGI Ref ID J:89373]

Jungnickel J; Klutzny A; Guhr S; Meyer K; Grothe C. 2005. Regulation of neuronal death and calcitonin gene-related peptide by fibroblast growth factor-2 and FGFR3 after peripheral nerve injury: evidence from mouse mutants. Neuroscience 134(4):1343-50. [PubMed: 16009496]  [MGI Ref ID J:104421]

Korada S; Zheng W; Basilico C; Schwartz ML; Vaccarino FM. 2002. Fibroblast growth factor 2 is necessary for the growth of glutamate projection neurons in the anterior neocortex. J Neurosci 22(3):863-75. [PubMed: 11826116]  [MGI Ref ID J:126973]

Lavine KJ; Yu K; White AC; Zhang X; Smith C; Partanen J; Ornitz DM. 2005. Endocardial and epicardial derived FGF signals regulate myocardial proliferation and differentiation in vivo. Dev Cell 8(1):85-95. [PubMed: 15621532]  [MGI Ref ID J:95803]

Li CF; Hughes-Fulford M. 2006. Fibroblast growth factor-2 is an immediate-early gene induced by mechanical stress in osteogenic cells. J Bone Miner Res 21(6):946-55. [PubMed: 16753025]  [MGI Ref ID J:128095]

Liao S; Porter D; Scott A; Newman G; Doetschman T; Schultz Jel J. 2007. The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: the role of JNK signaling. J Mol Cell Cardiol 42(1):106-20. [PubMed: 17150229]  [MGI Ref ID J:119652]

Montero A; Okada Y; Tomita M; Ito M; Tsurukami H; Nakamura T; Doetschman T; Coffin JD; Hurley MM. 2000. Disruption of the fibroblast growth factor-2 gene results in decreased bone mass and bone formation. J Clin Invest 105(8):1085-93. [PubMed: 10772653]  [MGI Ref ID J:78866]

Murtie JC; Zhou YX; Le TQ; Armstrong RC. 2005. In vivo analysis of oligodendrocyte lineage development in postnatal FGF2 null mice. Glia 49(4):542-54. [PubMed: 15578654]  [MGI Ref ID J:104940]

Murtie JC; Zhou YX; Le TQ; Vana AC; Armstrong RC. 2005. PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination. Neurobiol Dis 19(1-2):171-82. [PubMed: 15837572]  [MGI Ref ID J:105115]

Naganawa T; Xiao L; Abogunde E; Sobue T; Kalajzic I; Sabbieti M; Agas D; Hurley MM. 2006. In vivo and in vitro comparison of the effects of FGF-2 null and haplo-insufficiency on bone formation in mice. Biochem Biophys Res Commun 339(2):490-8. [PubMed: 16298332]  [MGI Ref ID J:103985]

Okada Y; Montero A; Zhang X; Sobue T; Lorenzo J; Doetschman T; Coffin JD; Hurley MM. 2003. Impaired osteoclast formation in bone marrow cultures of Fgf2 null mice in response to parathyroid hormone. J Biol Chem 278(23):21258-66. [PubMed: 12665515]  [MGI Ref ID J:133244]

Raballo R; Rhee J; Lyn-Cook R; Leckman JF; Schwartz ML; Vaccarino FM. 2000. Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex. J Neurosci 20(13):5012-23. [PubMed: 10864959]  [MGI Ref ID J:63176]

Reuss B; Dono R; Unsicker K. 2003. Functions of fibroblast growth factor (FGF)-2 and FGF-5 in astroglial differentiation and blood-brain barrier permeability: evidence from mouse mutants. J Neurosci 23(16):6404-12. [PubMed: 12878680]  [MGI Ref ID J:84705]

Schultz JE; Witt SA; Nieman ML; Reiser PJ; Engle SJ; Zhou M; Pawlowski SA; Lorenz JN; Kimball TR; Doetschman T. 1999. Fibroblast growth factor-2 mediates pressure-induced hypertrophic response. J Clin Invest 104(6):709-19. [PubMed: 10491406]  [MGI Ref ID J:57630]

Sullivan CJ; Doetschman T; Hoying JB. 2002. Targeted disruption of the Fgf2 gene does not affect vascular growth in the mouse ischemic hindlimb. J Appl Physiol 93(6):2009-17. [PubMed: 12391121]  [MGI Ref ID J:103383]

Sullivan CJ; Hoying JB. 2002. Flow-dependent remodeling in the carotid artery of fibroblast growth factor-2 knockout mice. Arterioscler Thromb Vasc Biol 22(7):1100-5. [PubMed: 12117723]  [MGI Ref ID J:103193]

Tanaka T; Saika S; Ohnishi Y; Ooshima A; McAvoy JW; Liu CY; Azhar M; Doetschman T; Kao WW. 2004. Fibroblast growth factor 2: roles of regulation of lens cell proliferation and epithelial-mesenchymal transition in response to injury. Mol Vis 10:462-7. [PubMed: 15273655]  [MGI Ref ID J:91701]

Timmer M; Cesnulevicius K; Winkler C; Kolb J; Lipokatic-Takacs E; Jungnickel J; Grothe C. 2007. Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the development of the substantia nigra, and FGF-2 plays a crucial role for the rescue of dopaminergic neurons after 6-hydroxydopamine lesion. J Neurosci 27(3):459-71. [PubMed: 17234579]  [MGI Ref ID J:117417]

Virag JA; Rolle ML; Reece J; Hardouin S; Feigl EO; Murry CE. 2007. Fibroblast growth factor-2 regulates myocardial infarct repair: effects on cell proliferation, scar contraction, and ventricular function. Am J Pathol 171(5):1431-40. [PubMed: 17872976]  [MGI Ref ID J:126804]

Yoshimura S; Takagi Y; Harada J; Teramoto T; Thomas SS; Waeber C; Bakowska JC; Breakefield XO; Moskowitz MA. 2001. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury. Proc Natl Acad Sci U S A 98(10):5874-9. [PubMed: 11320217]  [MGI Ref ID J:126024]

Zheng W; Nowakowski RS; Vaccarino FM. 2004. Fibroblast growth factor 2 is required for maintaining the neural stem cell pool in the mouse brain subventricular zone. Dev Neurosci 26(2-4):181-96. [PubMed: 15711059]  [MGI Ref ID J:104899]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. 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
	Wild-type from the colony
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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“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.”

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