Strain Name:

BTBR-Pahenu2/J

Stock Number:

002232

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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

Type Chemically Induced Mutation; Mutant Strain;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Alexandra Shedlovsky,   University of Wisconsin , Madison

Appearance
black and tan, tufted
Related Genotype: at/at +T/+T tf/tf

Description
Homozygous mutant mice show severe hyperphenylalanemia. They are hypopigmented unless maintained on a low phenylalanine diet. Females are fertile but do not rear their young when maintained on a standard mouse diet. The coat color of the background strain, BTBR +T tf/tf, is black and tan (at/at). This strain is also homozygous for the gene tufted (tf/tf) resulting in various molting patterns in the mouse coat. These effects, limited to the mouse coat, may make the mice appear malformed.

Development
This strain was developed in the laboratory of Dr. Alexandra Shedlovsky at the McArdle Laboratory for Cancer Research, University of Wisconsin. The mutation was generated by ENU treatment of BTBR +T tf/tf males.

Control Information

  Control
   002282 BTBR T+ Itpr3tf/J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Pah
002231   BTBR.Cg-Pahenu1/J
View Strains carrying other alleles of Pah     (1 strain)

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).
Phenylketonuria; PKU
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Pahenu2/Pahenu2

        involves: BTBR
  • homeostasis/metabolism phenotype
  • abnormal circulating amino acid level
    • serum phenylalanine levels elevated 10-20X on a normal diet   (MGI Ref ID J:13320)
  • abnormal response/metabolism to endogenous compounds
    • animals sicken after a few days on elevated phenylalanine (in drinking water)   (MGI Ref ID J:13320)
  • abnormal serotonin level
    • reduced 70% in the brain   (MGI Ref ID J:89662)
  • abnormal urine homeostasis
    • phenylketones in urine greatly elevated   (MGI Ref ID J:13320)
  • growth/size/body phenotype
  • microcephaly
    • small heads   (MGI Ref ID J:13320)
  • postnatal growth retardation   (MGI Ref ID J:13320)
    • body weights diverged from controls starting at week 1 and continuing through week 7   (MGI Ref ID J:66447)
    • weight divergence as much as 30%   (MGI Ref ID J:66447)
  • behavior/neurological phenotype
  • abnormal learning/memory/conditioning
    • absence of latent learning   (MGI Ref ID J:56815)
    • abnormal olfactory -discrimination memory
      • odor discrimination learning was normal but reverse descrimination training was deficient   (MGI Ref ID J:56815)
  • abnormal sensory capabilities/reflexes/nociception
    • appear to be less alert   (MGI Ref ID J:13320)
  • impaired balance
    • tend to topple over while grooming themselves   (MGI Ref ID J:13320)
  • impaired swimming
    • uncoordinated in swim tests   (MGI Ref ID J:13320)
  • pigmentation phenotype
  • hypopigmentation
    • beginning at 2 weeks and worsening until 5-6 weeks of age   (MGI Ref ID J:13320)
  • reproductive system phenotype
  • decreased litter size
    • average litter size at birth normal but pups die within a few hours   (MGI Ref ID J:13320)
    • survival improves when cross fostered to a "wild-type" mother   (MGI Ref ID J:13320)
  • renal/urinary system phenotype
  • abnormal urine homeostasis
    • phenylketones in urine greatly elevated   (MGI Ref ID J:13320)

Pahenu2/Pahenu2

        BTBR-Pahenu2/J
  • homeostasis/metabolism phenotype
  • abnormal amino acid level
    • mutants exhibit an increase in phenylalanine concentration in the cerebral cortex   (MGI Ref ID J:178269)
  • abnormal enzyme/ coenzyme level
    • the cerebral cortex exhibits increased NADPH oxidase activity   (MGI Ref ID J:178269)
  • nervous system phenotype
  • abnormal cerebral cortex morphology
    • mutants exhibit an increase in phenylalanine concentration in the cerebral cortex   (MGI Ref ID J:178269)
View Research Applications

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

Pahenu2 related

Metabolism Research

Neurobiology Research
Metabolic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Pahenu2
Allele Name phenylalanine hydroxylase enu 2
Allele Type Chemically induced (ENU)
Common Name(s) HPH5.1;
Mutation Made ByDr. William Dove,   University of Wisconsin- Madison
Strain of OriginBTBR
Gene Symbol and Name Pah, phenylalanine hydroxylase
Chromosome 10
Gene Common Name(s) AW106920; PH; PKU; PKU1; expressed sequence AW106920;
Molecular Note A T835C missense mutation in exon 7 results in a phenylalanine to serine substitution at amino acid 263 (F263S). [MGI Ref ID J:38411]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Shedlovsky A; McDonald JD; Symula D; Dove WF. 1993. Mouse models of human phenylketonuria. Genetics 134(4):1205-10. [PubMed: 8375656]  [MGI Ref ID J:13320]

Additional References

Ercal N; Aykin-Burns N; Gurer-Orhan H; McDonald JD. 2002. Oxidative stress in a phenylketonuria animal model. Free Radic Biol Med 32(9):906-11. [PubMed: 11978492]  [MGI Ref ID J:77922]

Gropper SS; Yannicelli S; White BD; Medeiros DM. 2004. Plasma phenylalanine concentrations are associated with hepatic iron content in a murine model for phenylketonuria. Mol Genet Metab 82(1):76-82. [PubMed: 15110326]  [MGI Ref ID J:91053]

Kornguth S; Anderson M; Markley JL; Shedlovsky A. 1994. Near-microscopic magnetic resonance imaging of the brains of phenylalanine hydroxylase-deficient mice, normal littermates, and of normal BALB/c mice at 9.4 Tesla. Neuroimage 1(3):220-9. [PubMed: 9343573]  [MGI Ref ID J:44995]

McDonald JD; Charlton CK. 1997. Characterization of mutations at the mouse phenylalanine hydroxylase locus. Genomics 39(3):402-5. [PubMed: 9119379]  [MGI Ref ID J:38411]

Smith CB; Kang J. 2000. Cerebral protein synthesis in a genetic mouse model of phenylketonuria Proc Natl Acad Sci U S A 97(20):11014-9. [PubMed: 11005872]  [MGI Ref ID J:64741]

Zagreda L; Goodman J; Druin DP; McDonald D; Diamond A. 1999. Cognitive deficits in a genetic mouse model of the most common biochemical cause of human mental retardation. J Neurosci 19(14):6175-82. [PubMed: 10407053]  [MGI Ref ID J:56815]

Pahenu2 related

Cabib S; Pascucci T; Ventura R; Romano V; Puglisi-Allegra S. 2003. The behavioral profile of severe mental retardation in a genetic mouse model of phenylketonuria. Behav Genet 33(3):301-10. [PubMed: 12837019]  [MGI Ref ID J:83609]

Cho S; McDonald JD. 2001. Effect of maternal blood phenylalanine level on mouse maternal phenylketonuria offspring. Mol Genet Metab 74(4):420-5. [PubMed: 11749047]  [MGI Ref ID J:101674]

Christensen R; Alhonen L; Wahlfors J; Jakobsen M; Jensen TG. 2005. Characterization of transgenic mice with the expression of phenylalanine hydroxylase and GTP cyclohydrolase I in the skin. Exp Dermatol 14(7):535-42. [PubMed: 15946242]  [MGI Ref ID J:137411]

Dyer CA; Kendler A; Philibotte T; Gardiner P; Cruz J; Levy HL. 1996. Evidence for central nervous system glial cell plasticity in phenylketonuria. J Neuropathol Exp Neurol 55(7):795-814. [PubMed: 8965095]  [MGI Ref ID J:121248]

Embury JE; Charron CE; Martynyuk A; Zori AG; Liu B; Ali SF; Rowland NE; Laipis PJ. 2007. PKU is a reversible neurodegenerative process within the nigrostriatum that begins as early as 4 weeks of age in Pah(enu2) mice. Brain Res 1127(1):136-50. [PubMed: 17112485]  [MGI Ref ID J:116603]

Embury JE; Reep RR; Laipis PJ. 2005. Pathologic and immunohistochemical findings in hypothalamic and mesencephalic regions in the pah(enu2) mouse model for phenylketonuria. Pediatr Res 58(2):283-7. [PubMed: 16055931]  [MGI Ref ID J:110423]

Ercal N; Aykin-Burns N; Gurer-Orhan H; McDonald JD. 2002. Oxidative stress in a phenylketonuria animal model. Free Radic Biol Med 32(9):906-11. [PubMed: 11978492]  [MGI Ref ID J:77922]

Gropper SS; Yannicelli S; White BD; Medeiros DM. 2004. Plasma phenylalanine concentrations are associated with hepatic iron content in a murine model for phenylketonuria. Mol Genet Metab 82(1):76-82. [PubMed: 15110326]  [MGI Ref ID J:91053]

Hamman KJ; Winn SR; Harding CO. 2011. Hepatocytes from wild-type or heterozygous donors are equally effective in achieving successful therapeutic liver repopulation in murine phenylketonuria (PKU). Mol Genet Metab 104(3):235-40. [PubMed: 21917493]  [MGI Ref ID J:178220]

Harding CO; Wild K; Chang D; Messing A; Wolff JA. 1998. Metabolic engineering as therapy for inborn errors of metabolism--development of mice with phenylalanine hydroxylase expression in muscle. Gene Ther 5(5):677-83. [PubMed: 9797873]  [MGI Ref ID J:47853]

Kornguth S; Anderson M; Markley JL; Shedlovsky A. 1994. Near-microscopic magnetic resonance imaging of the brains of phenylalanine hydroxylase-deficient mice, normal littermates, and of normal BALB/c mice at 9.4 Tesla. Neuroimage 1(3):220-9. [PubMed: 9343573]  [MGI Ref ID J:44995]

Lu L; Gu X; Li D; Liang L; Zhao Z; Gao J. 2011. Mechanisms regulating superoxide generation in experimental models of phenylketonuria: an essential role of NADPH oxidase. Mol Genet Metab 104(3):241-8. [PubMed: 21640623]  [MGI Ref ID J:178269]

Matalon R; Surendran S; McDonald JD; Okorodudu AO; Tyring SK; Michals-Matalon K; Harris P. 2005. Abnormal expression of genes associated with development and inflammation in the heart of mouse maternal phenylketonuria offspring. Int J Immunopathol Pharmacol 18(3):557-65. [PubMed: 16164837]  [MGI Ref ID J:106344]

McDonald JD. 2000. Postnatal growth in a mouse genetic model of classical phenylketonuria Contemp Topics 39(6):54-56.  [MGI Ref ID J:66447]

McDonald JD; Charlton CK. 1997. Characterization of mutations at the mouse phenylalanine hydroxylase locus. Genomics 39(3):402-5. [PubMed: 9119379]  [MGI Ref ID J:38411]

Ney DM; Hull AK; van Calcar SC; Liu X; Etzel MR. 2008. Dietary glycomacropeptide supports growth and reduces the concentrations of phenylalanine in plasma and brain in a murine model of phenylketonuria. J Nutr 138(2):316-22. [PubMed: 18203898]  [MGI Ref ID J:133408]

Oh HJ; Lee H; Park JW; Rhee H; Koo SK; Kang S; Jo I; Jung SC. 2005. Reversal of gene expression profile in the phenylketonuria mouse model after adeno-associated virus vector-mediated gene therapy. Mol Genet Metab 86 Suppl 1:S124-32. [PubMed: 16150627]  [MGI Ref ID J:104163]

Okano HJ; Darnell RB. 1997. A hierarchy of Hu RNA binding proteins in developing and adult neurons. J Neurosci 17(9):3024-37. [PubMed: 9096138]  [MGI Ref ID J:62325]

Pascucci T; Andolina D; Ventura R; Puglisi-Allegra S; Cabib S. 2008. Reduced availability of brain amines during critical phases of postnatal development in a genetic mouse model of cognitive delay. Brain Res 1217:232-8. [PubMed: 18502400]  [MGI Ref ID J:138380]

Pascucci T; Giacovazzo G; Andolina D; Accoto A; Fiori E; Ventura R; Orsini C; Conversi D; Carducci C; Leuzzi V; Puglisi-Allegra S. 2013. Behavioral and neurochemical characterization of new mouse model of hyperphenylalaninemia. PLoS One 8(12):e84697. [PubMed: 24376837]  [MGI Ref ID J:209846]

Pascucci T; Ventura R; Puglisi-Allegra S; Cabib S. 2002. Deficits in brain serotonin synthesis in a genetic mouse model of phenylketonuria. Neuroreport 13(18):2561-4. [PubMed: 12499868]  [MGI Ref ID J:89662]

Puglisi-Allegra S; Cabib S; Pascucci T; Ventura R; Cali F; Romano V. 2000. Dramatic brain aminergic deficit in a genetic mouse model of phenylketonuria. Neuroreport 11(6):1361-4. [PubMed: 10817622]  [MGI Ref ID J:103668]

Sarkissian CN; Boulais DM; McDonald JD; Scriver CR. 2000. A heteroallelic mutant mouse model: A new orthologue for human hyperphenylalaninemia. Mol Genet Metab 69(3):188-94. [PubMed: 10767173]  [MGI Ref ID J:62365]

Seagraves NJ; McBride KL. 2012. Cardiac teratogenicity in mouse maternal phenylketonuria: Defining phenotype parameters and genetic background influences. Mol Genet Metab 107(4):650-8. [PubMed: 22951387]  [MGI Ref ID J:190148]

Sidell N; Hao L; Pasquali M; McDonald JD. 2009. Carcinogenic effects in a phenylketonuria mouse model. PLoS ONE 4(1):e4292. [PubMed: 19172175]  [MGI Ref ID J:144837]

Smith CB; Kang J. 2000. Cerebral protein synthesis in a genetic mouse model of phenylketonuria Proc Natl Acad Sci U S A 97(20):11014-9. [PubMed: 11005872]  [MGI Ref ID J:64741]

Solverson P; Murali SG; Litscher SJ; Blank RD; Ney DM. 2012. Low bone strength is a manifestation of phenylketonuria in mice and is attenuated by a glycomacropeptide diet. PLoS One 7(9):e45165. [PubMed: 23028819]  [MGI Ref ID J:191864]

Zagreda L; Goodman J; Druin DP; McDonald D; Diamond A. 1999. Cognitive deficits in a genetic mouse model of the most common biochemical cause of human mental retardation. J Neurosci 19(14):6175-82. [PubMed: 10407053]  [MGI Ref ID J:56815]

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 & HusbandryThis strain is maintained by breeding heterozygous females to homozygous males. Heterozygous and homozygous mice may be ordered. Technician's Note: This strain breeds well and does not require any special husbandry. The Jackson Laboratory maintains their colony on a 6% fat diet. The average litter size is 8-12 pups. Expected coat color from breeding:Black with Brown

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

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.

Frozen Products

Price (US dollars $)
Frozen Embryo $1650.00

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 10 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 View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

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.

Frozen Products

Price (US dollars $)
Frozen Embryo $2145.00

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 10 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).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   002282 BTBR T+ Itpr3tf/J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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