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. Species laboratory mouse Generation F?+18p   Donating Investigator Alexandra Shedlovsky,   University of Wisconsin

Appearance
black and tan, tufted
Related Genotype: a^t/a^t +^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 (a^t/a^t). 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+ tf/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

Phenylketonuria; PKU - 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

Pah^enu2/Pah^enu2

        involves: BTBR

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

View Research Applications

Research Applications

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

Pah^enu2 related

Metabolism Research

Mouse/Human Gene Homologs
phenylketonuria

Neurobiology Research
Metabolic Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pahenu2
Allele Name		phenylalanine hydroxylase enu 2
Allele Type		Chemically induced (ENU)
Common Name(s)		HPH5.1;
Mutation Made By		William Dove,   University of Wisconsin
Strain of Origin		BTBR
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

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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]

Pah^enu2 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]

Chen L; Woo SL. 2005. Complete and persistent phenotypic correction of phenylketonuria in mice by site-specific genome integration of murine phenylalanine hydroxylase cDNA. Proc Natl Acad Sci U S A 102(43):15581-6. [PubMed: 16230623]  [MGI Ref ID J:102484]

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]

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]

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; 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]

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]

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

Colony Maintenance

Breeding & Husbandry	This 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

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. 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 from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. 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. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	002282 BTBR T+ tf/J
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

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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

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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.”

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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.

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