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Former Names B6 x C57BLKS-Pitx3ak/J (Changed: 04-MAY-05 ) Type Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N6p
Generation DefinitionsDescription
Mice homozygous for the Pitx3ak mutation exhibit microphthalmia (small eyes) and aphakia (no lens) related to arrested lens development. The mesencephalic dopamine system is malformed and as a result homozygotes fail to develop dopaminergic neurons of the substantia nigra (Smidt et al., 2004). Homozygotes display sensorimotor deficits specific to the nigrostriatal pathway such as the challenge beam and pole test and the test for spontaneous exploratory activitiy in a cylinder. These deficits can be reversed by L-DOPA administration (Hwang et al., 2005). This mutant mouse strain may be useful in studies of Parkinson's disease.Development
The aphakia allele arose spontaneously in 1981 on the 129S1/Sv-p+ Tyr+ KitlSl-J/J strain. A female with a small right eye was mated to a male with small left eye (male 1). The mating produced greater than 50% bilaterally aphakic pups. As a result of poor breeding on the original129S1 background, male 1 was mated to a C57BLKS/J female. The one F1 aphakic female produced was used to build the colony. The colony was maintained by occasional crossing to C57BLKS/J (Varnum et al. 1968). This strain was cryopreserved in 1984 using homozygous males at generation N5F39 or N5F40 bred to C57BL/6J females. The strain was cryo-recovered in 2005.
| Control | ||
|---|---|---|
| Heterozygote from the colony | ||
| Considerations for Choosing Controls | ||
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
Strains carrying other alleles of Pitx3
022306 B6N(Cg)-Pitx3tm1.1(KOMP)Vlcg/J View Strains carrying other alleles of Pitx3 (1 strain)
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
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).
Anterior Segment Mesenchymal Dysgenesis; ASMD
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Cataract 11, Multiple Types; CTRCT11 (PITX3)
Paired-Like Homeodomain Transcription Factor 3; PITX3 (PITX3)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Pitx3ak/Pitx3ak
involves: 129S1/Sv * C57BL/6 * C57BLKS/J
- nervous system phenotype
- abnormal dorsal striatum morphology
- results using the key dopamine neuronal marker, TH, suggest a reduction of neurons in the dorsal striatum, however, not in the nucleus accumbens or olfactory tubercle implying a defective nigrostriatal pathway (MGI Ref ID J:109319)
- abnormal substantia nigra morphology
- Nissl staining indicates that cell density is dramatically reduced in the substantia nigra pas as compared to wild-type (MGI Ref ID J:109319)
- dopaminergic neurons remaining in the substantia nigra appear atrophic with somewhat shrunken cell bodies (MGI Ref ID J:109319)
- results using both the key dopamine neuronal marker, TH, and Fluorogold retrograde labeling suggest the absence of dopaminergic neurons in the substantia nigra pas compacta indicating that nigrostriatal projections do not develop (MGI Ref ID J:109319)
- neuron loss is apparent in newborn mice (MGI Ref ID J:109319)
- decreased dopamine level
- levels are reduced to 10% of wildtype in the dorsal striatum, however levels in the ventral striatum are not affected (MGI Ref ID J:109319)
- loss of dopaminergic neurons
- selective loss of A9 dopaminergic neurons in the substantia nigra; A10 neurons in the ventral tegmental area appear to be intact (MGI Ref ID J:109319)
- behavior/neurological phenotype
- abnormal locomotor behavior
- higher ambulatory activity than control during lights-on period, however, lower ambulatory activity than control during lights-off period (MGI Ref ID J:98209)
- decreased vertical activity
- mice exhibit a decrease in rearing and hindlimb stepping as measured in the transparent cylinder, however, administration of L-DOPA increases spontaneous activity to the same or higher than wildtype (MGI Ref ID J:98209)
- hyperactivity
- total horizontal movements during a 22 hour period are slightly increased over that of control (MGI Ref ID J:98209)
- impaired coordination
- mice exhibit longer times to traverse a balance beam challenge and a 25% increase in the number of steps as compared to controls, however, administration of L-DOPA reduced beam time and step number almost to wild-type levels (MGI Ref ID J:98209)
- in a vertical pole test, mice take longer than controls to orient downwards; L-DOPA administration reduces orientation time (MGI Ref ID J:98209)
- homeostasis/metabolism phenotype
- decreased dopamine level
- levels are reduced to 10% of wildtype in the dorsal striatum, however levels in the ventral striatum are not affected (MGI Ref ID J:109319)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Pitx3ak/Pitx3ak
either: (involves: 129/Sv * C57BLKS) or (involves: 129/Sv * C57BL/6)
- pigmentation phenotype
- abnormal iris pigmentation
- behavior/neurological phenotype
- hypoactivity
- reduced spontaneous activity at night (MGI Ref ID J:82907)
- endocrine/exocrine gland phenotype
- abnormal lacrimal gland morphology
- enlarged lacrimal gland partially fills the orbit (MGI Ref ID J:5084)
- growth/size phenotype
- decreased body size
- slightly smaller than normal (MGI Ref ID J:5084)
- reproductive system phenotype
- reduced fertility
- fertility is reduced at generation F3 and beyond, particularly for females (MGI Ref ID J:5084)
- vision/eye phenotype
- abnormal anterior eye segment morphology (MGI Ref ID J:5084)
- abnormal eye distance/ position
- ocular area slightly concave after eyes open (MGI Ref ID J:5084)
- abnormal lacrimal gland morphology
- enlarged lacrimal gland partially fills the orbit (MGI Ref ID J:5084)
- abnormal posterior eye segment morphology (MGI Ref ID J:5084)
- microphthalmia
- nervous system phenotype
- abnormal midbrain morphology
- less cellularity in the substantia nigra (MGI Ref ID J:82746)
- tyrosine hydroxylase immunoreactivity absent in the substantia nigra (MGI Ref ID J:82746)
- decreased numbers of nigrostriatal fibers (MGI Ref ID J:82746)
- at E12.5, mesencephalon dopaminergic neurons are normal (MGI Ref ID J:82907)
- by the first day after birth there is a 91% reduction in neurons with tyrosine hydroxylase immunoreactivity (MGI Ref ID J:82907)
- reduced activity in the ventral tegmental area but slower to develop (MGI Ref ID J:82907)
- dorsal tier of the pars compacta of the substantia nigra retains tyrosine hydroxylase activity (MGI Ref ID J:82907)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Pitx3ak related
Neurobiology Research
Parkinson's Disease
Sensorineural Research
Cataracts
cortical
| Allele Symbol | Pitx3ak | ||
|---|---|---|---|
| Allele Name | aphakia | ||
| Allele Type | Spontaneous | ||
| Common Name(s) | ak; | ||
| Strain of Origin | 129S1/Sv-Kitl | ||
| Gene Symbol and Name | Pitx3, paired-like homeodomain transcription factor 3 | ||
| Chromosome | 19 | ||
| Gene Common Name(s) | CTPP4; CTRCT11; PTX3; ak; aphakia; | ||
| General Note | Phenotypic Similarity to Human Syndrome: Parkinson Disease (J:98209, J:104915) | ||
| Molecular Note | This allele carries a 652 bp deletion in the promoter region of the gene, located 2.5 kb upstream of the transcription start site. The deletion cosegregated with the aphakia phenotype. In situ hybridization studies of homozygous mutant mice did not detect transcripts in the lens placode or at later developmental stages of the lens. [MGI Ref ID J:63167] [MGI Ref ID J:68175] | ||
Varnum DS; Stevens LC. 1968. Aphakia, a new mutation in the mouse. J Hered 59(2):147-50. [PubMed: 4970465] [MGI Ref ID J:5084]
Smidt MP; Smits SM; Bouwmeester H; Hamers FP; van der Linden AJ; Hellemons AJ; Graw J; Burbach JP. 2004. Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3. Development 131(5):1145-55. [PubMed: 14973278] [MGI Ref ID J:88592]
Pitx3ak relatedArdayfio P; Moon J; Leung KK; Youn-Hwang D; Kim KS. 2008. Impaired learning and memory in Pitx3 deficient aphakia mice: A genetic model for striatum-dependent cognitive symptoms in Parkinson's disease. Neurobiol Dis :. [PubMed: 18573342] [MGI Ref ID J:136304]
Ardayfio PA; Leung A; Park J; Hwang DY; Moran-Gates T; Choi YK; Carlezon WA Jr; Tarazi FI; Kim KS. 2010. Pitx3-deficient aphakia mice display unique behavioral responses to psychostimulant and antipsychotic drugs. Neuroscience 166(2):391-6. [PubMed: 20026251] [MGI Ref ID J:159741]
Coulon V; L'Honore A; Ouimette JF; Dumontier E; van den Munckhof P; Drouin J. 2007. A muscle-specific promoter directs Pitx3 gene expression in skeletal muscle cells. J Biol Chem 282(45):33192-200. [PubMed: 17848564] [MGI Ref ID J:126948]
Ding Y; Restrepo J; Won L; Hwang DY; Kim KS; Kang UJ. 2007. Chronic 3,4-dihydroxyphenylalanine treatment induces dyskinesia in aphakia mice, a novel genetic model of Parkinson's disease. Neurobiol Dis 27(1):11-23. [PubMed: 17499513] [MGI Ref ID J:122000]
Ding Y; Won L; Britt JP; Lim SA; McGehee DS; Kang UJ. 2011. Enhanced striatal cholinergic neuronal activity mediates L-DOPA-induced dyskinesia in parkinsonian mice. Proc Natl Acad Sci U S A 108(2):840-5. [PubMed: 21187382] [MGI Ref ID J:170567]
Grimm C; Chatterjee B; Favor J; Immervoll T; Loster J; Klopp N; Sandulache R; Graw J. 1998. Aphakia (ak), a mouse mutation affecting early eye development: fine mapping, consideration of candidate genes and altered Pax6 and Six3 gene expression pattern. Dev Genet 23(4):299-316. [PubMed: 9883582] [MGI Ref ID J:51693]
Hwang DY; Ardayfio P; Kang UJ; Semina EV; Kim KS. 2003. Selective loss of dopaminergic neurons in the substantia nigra of Pitx3-deficient aphakia mice. Brain Res Mol Brain Res 114(2):123-31. [PubMed: 12829322] [MGI Ref ID J:109319]
Hwang DY; Fleming SM; Ardayfio P; Moran-Gates T; Kim H; Tarazi FI; Chesselet MF; Kim KS. 2005. 3,4-dihydroxyphenylalanine reverses the motor deficits in Pitx3-deficient aphakia mice: behavioral characterization of a novel genetic model of Parkinson's disease. J Neurosci 25(8):2132-7. [PubMed: 15728853] [MGI Ref ID J:98209]
Hwang DY; Hong S; Jeong JW; Choi S; Kim H; Kim J; Kim KS. 2009. Vesicular monoamine transporter 2 and dopamine transporter are molecular targets of Pitx3 in the ventral midbrain dopamine neurons. J Neurochem 111(5):1202-12. [PubMed: 19780901] [MGI Ref ID J:155057]
Jacobs FM; Smits SM; Noorlander CW; von Oerthel L; van der Linden AJ; Burbach JP; Smidt MP. 2007. Retinoic acid counteracts developmental defects in the substantia nigra caused by Pitx3 deficiency. Development 134(14):2673-84. [PubMed: 17592014] [MGI Ref ID J:122792]
Jacobs FM; Veenvliet JV; Almirza WH; Hoekstra EJ; von Oerthel L; van der Linden AJ; Neijts R; Koerkamp MG; van Leenen D; Holstege FC; Burbach JP; Smidt MP. 2011. Retinoic acid-dependent and -independent gene-regulatory pathways of Pitx3 in meso-diencephalic dopaminergic neurons. Development 138(23):5213-22. [PubMed: 22069189] [MGI Ref ID J:178682]
Kas MJ; van der Linden AJ; Oppelaar H; von Oerthel L; Ramakers GM; Smidt MP. 2008. Phenotypic segregation of aphakia and Pitx3-null mutants reveals that Pitx3 deficiency increases consolidation of specific movement components Behav Brain Res 186(2):208-14. [PubMed: 17919745] [MGI Ref ID J:125552]
Kim J; Inoue K; Ishii J; Vanti WB; Voronov SV; Murchison E; Hannon G; Abeliovich A. 2007. A MicroRNA feedback circuit in midbrain dopamine neurons. Science 317(5842):1220-4. [PubMed: 17761882] [MGI Ref ID J:125222]
Lennington JB; Pope S; Goodheart AE; Drozdowicz L; Daniels SB; Salamone JD; Conover JC. 2011. Midbrain dopamine neurons associated with reward processing innervate the neurogenic subventricular zone. J Neurosci 31(37):13078-87. [PubMed: 21917791] [MGI Ref ID J:177043]
Medina-Martinez O; Shah R; Jamrich M. 2009. Pitx3 controls multiple aspects of lens development. Dev Dyn 238(9):2193-2201. [PubMed: 19334279] [MGI Ref ID J:151273]
Nunes I; Tovmasian LT; Silva RM; Burke RE; Goff SP. 2003. Pitx3 is required for development of substantia nigra dopaminergic neurons. Proc Natl Acad Sci U S A 100(7):4245-50. [PubMed: 12655058] [MGI Ref ID J:82746]
Papanikolaou T; Amano T; Lennington J; Sink K; Farrar AM; Salamone J; Yang X; Conover JC. 2009. In-vitro analysis of Pitx3 in mesodiencephalic dopaminergic neuron maturation. Eur J Neurosci 29(12):2264-75. [PubMed: 19508691] [MGI Ref ID J:151532]
Rieger DK; Reichenberger E; McLean W; Sidow A; Olsen BR. 2001. A double-deletion mutation in the pitx3 gene causes arrested lens development in aphakia mice. Genomics 72(1):61-72. [PubMed: 11247667] [MGI Ref ID J:68175]
Rosemann M; Ivashkevich A; Favor J; Dalke C; Holter SM; Becker L; Racz I; Bolle I; Klempt M; Rathkolb B; Kalaydjiev S; Adler T; Aguilar A; Hans W; Horsch M; Rozman J; Calzada-Wack J; Kunder S; Naton B; Gailus-Durner V; Fuchs H; Schulz H; Beckers J; BuschDH; Burbach JP; Smidt MP; Quintanilla-Martinez L; Esposito I; Klopstock T; Klingenspor M; Ollert M; Wolf E; Wurst W; Zimmer A; Hrabe de Angelis M; Atkinson M; Heinzmann U; Graw J. 2010. Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 ( 416insG ) mice. Mamm Genome 21(1-2):13-27. [PubMed: 20033184] [MGI Ref ID J:156878]
Semina EV; Murray JC; Reiter R; Hrstka RF; Graw J. 2000. Deletion in the promoter region and altered expression of pitx3 homeobox gene in aphakia mice Hum Mol Genet 9(11):1575-85. [PubMed: 10861284] [MGI Ref ID J:63167]
Singh B; Wilson JH; Vasavada HH; Guo Z; Allore HG; Zeiss CJ. 2007. Motor deficits and altered striatal gene expression in aphakia (ak) mice. Brain Res 1185:283-92. [PubMed: 17949697] [MGI Ref ID J:128707]
Smits SM; Mathon DS; Burbach JP; Ramakers GM; Smidt MP. 2005. Molecular and cellular alterations in the Pitx3-deficient midbrain dopaminergic system. Mol Cell Neurosci 30(3):352-63. [PubMed: 16140547] [MGI Ref ID J:102233]
Smits SM; van der Nobelen S; Hornman KJ; von Oerthel L; Burbach JP; Smidt MP. 2005. Signalling through phospholipase C beta 4 is not essential for midbrain dopaminergic neuron survival. Neuroscience 136(1):171-9. [PubMed: 16198487] [MGI Ref ID J:104551]
Varnum DS; Stevens LC. 1975. Aphakia linked with brachymorphic. Mouse News Lett 53:35. [MGI Ref ID J:13685]
Webster EH Jr; Zwaan J; Cooper P. 1986. Abnormal accumulation of sulphated materials in lens tissue of mice with the aphakia mutation. J Embryol Exp Morphol 92:85-101. [PubMed: 3522797] [MGI Ref ID J:8330]
Zwaan J. 1975. Immunofluorescent studies on aphakia, a mutation of a gene involved in the control of lens differentiation in the mouse embryo. Dev Biol 44(2):306-12. [PubMed: 1093912] [MGI Ref ID J:5541]
Zwaan J; Kirkland BM. 1975. Malorientation of mitotic figures in the early lens rudiment of aphakia mouse embryos. Anat Rec 182(3):345-54. [PubMed: 1155804] [MGI Ref ID J:5562]
Zwaan J; Webster EH Jr. 1984. Histochemical analysis of extracellular matrix material during embryonic mouse lens morphogenesis in an aphakic strain of mice. Dev Biol 104(2):380-9. [PubMed: 6745489] [MGI Ref ID J:7505]
de Rover M; Lodder JC; Smidt MP; Brussaard AB. 2006. Pitx3 deficiency in mice affects cholinergic modulation of GABAergic synapses in the nucleus accumbens. J Neurophysiol 96(4):2034-41. [PubMed: 16837663] [MGI Ref ID J:135703]
van den Munckhof P; Gilbert F; Chamberland M; Levesque D; Drouin J. 2006. Striatal neuroadaptation and rescue of locomotor deficit by L-dopa in aphakia mice, a model of Parkinson's disease. J Neurochem 96(1):160-70. [PubMed: 16269007] [MGI Ref ID J:104915]
van den Munckhof P; Luk KC; Ste-Marie L; Montgomery J; Blanchet PJ; Sadikot AF; Drouin J. 2003. Pitx3 is required for motor activity and for survival of a subset of midbrain dopaminergic neurons. Development 130(11):2535-42. [PubMed: 12702666] [MGI Ref ID J:82907]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3175.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $4127.50 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| Heterozygote from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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