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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Allan Bradley,   Baylor College of Medicine

Description
Mice homozygous for this mutation are viable and fertile although about 65% of homozygous mice die by 4 weeks of age unless maintained on allopurinol. Homozygous mice show severe hyperuricemia and urate nephropathy.

Development
Exon 3 of the Uox gene was disrupted using a vector containing the neo resistance gene. The 129-derived AB1 ES cell line was used.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Uox

001378

B6;D2-In(3)55Rk Uoxin/J

View Strains carrying other alleles of Uox     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

	Diabetes Insipidus, Nephrogenic, Autosomal - Models with phenotypic similarity to human disease where etiologies are distinct.2
	Hyperuricemic Nephropathy, Familial Juvenile; HNFJ - Models with phenotypic similarity to human disease where etiologies are distinct.2

2 Human genes are associated with this disease. Orthologs of those genes do not appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Uox^tm1Bay/Uox^tm1Bay

        involves: 129S7/SvEvBrd * C57BL/6J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:16490)
  • 65% die within 4 weeks of age on the mixed 129S7/SvEvBrd and C57BL/6J background while a higher rate of lethality is seen on a 129/Sv background
• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:16490)
  • develop hyperuricemia, with 10-fold higher levels of serum uric acid levels
• increased blood urea nitrogen level (MGI Ref ID J:103187)
  • serum urea nitrogen concentrations at 50-60 days and 9-13 months of age are 1.5- and 2-fold, respectively, higher than in controls
• abnormal urine chemistry (MGI Ref ID J:16490)
  • develop hyperuricosuria (10x more urinary uric acid than normal) and exhibit a decrease in allantoin
  • uric acid/creatine molar ratio in the urine is 30- to 100-fold higher
  • crystals appear rapidly as urine cools
• abnormal urine color (MGI Ref ID J:103187)
  • mutants as young as 10 to 12 days of age produce copious pale urine
• decreased urine osmolality (MGI Ref ID J:103187)
  • urine osmolality is much lower than in controls
  • ability to concentrate urine when deprived of water is severely impaired
• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:103187)
  • exhibit progressive destruction of the kidneys as early as 6 days after birth, showing small cortical cysts and white-yellow deposits (urate crystals) which persist until P14 and then gradually resolve
  • as disease progresses, affected kidneys become smaller, discolored (pale yellow) and soft
• abnormal nephron morphology (MGI Ref ID J:16490)
  • glomeruli are associated with foci of tubular atrophy and collapse of the nephron
• abnormal renal glomerulus morphology (MGI Ref ID J:16490)
  • glomerular atrophy
  • kidneys exhibit tubular atrophy with apparent crowding of glomeruli
• abnormal renal tubule morphology (MGI Ref ID J:16490)
  • tubular degeneration and regeneration with dilation of tubules are seen at P8
  • exhibit mechanical blockage of renal tubules by urate crystal deposition within tubular lumens
  • kidneys exhibit tubular atrophy
• dilated renal tubules (MGI Ref ID J:16490)
  • dilation of tubules at P8
• dilated renal glomerular capsule (MGI Ref ID J:16490)
  • dilation of Bowman's spaces
• dilated kidney collecting duct (MGI Ref ID J:103187)
  • in both the cortex and medulla, collecting ducts are markedly dilated
• hydronephrosis (MGI Ref ID J:16490)
  • as obstructive disease progresses, hydronephrotic lesions appear and result in hydronephrosis at 5 weeks
  • exhibit scarred, irregularly shaped, hydronephrotic kidneys
• kidney cysts (MGI Ref ID J:16490)
  • the surface of the kidney becomes irregular with obvious pits and scars and multiple cysts
• kidney cortex cysts (MGI Ref ID J:16490)
  • cortical cysts start as dilations within the collecting tubules and extend from the papilla to the corticomedullary junction
• renal fibrosis (MGI Ref ID J:103187)
  • kidneys exhibit cortical foci of fibrosis
• small kidney (MGI Ref ID J:16490)
  • as disease progresses, affected kidneys become smaller
• abnormal kidney physiology (MGI Ref ID J:103187)
  • exhibit moderate azotemia, however do not observe signs of renal insufficiency
• polyuria (MGI Ref ID J:103187)
  • exhibit about 6-fold more urine output
• abnormal urinary bladder morphology (MGI Ref ID J:103187)
  • bladders of some adults are dilated and contain uric acid stones
• abnormal urine chemistry (MGI Ref ID J:16490)
  • develop hyperuricosuria (10x more urinary uric acid than normal) and exhibit a decrease in allantoin
  • uric acid/creatine molar ratio in the urine is 30- to 100-fold higher
  • crystals appear rapidly as urine cools
• abnormal urine color (MGI Ref ID J:103187)
  • mutants as young as 10 to 12 days of age produce copious pale urine
• decreased urine osmolality (MGI Ref ID J:103187)
  • urine osmolality is much lower than in controls
  • ability to concentrate urine when deprived of water is severely impaired
• kidney stones (MGI Ref ID J:103187)
  • bladders of some adults contain uric acid stones
• immune system phenotype
• chronic inflammation (MGI Ref ID J:16490)
  • chronic inflammation, characterized by infiltration of plasma cells, lymphocytes, and macrophages, occurs within the interstitium of the kidney
• behavior/neurological phenotype
• polydipsia (MGI Ref ID J:103187)
  • ingest about 5-fold more water

View Research Applications

Research Applications

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

Uox^tm1Bay related

Metabolism Research
Hyperuricemia (gout)

Genes & Alleles

Gene & Allele Information

Allele Symbol		Uoxtm1Bay
Allele Name		targeted mutation 1, Baylor College of Medicine
Allele Type		Targeted (knock-out)
Mutation Made By		Allan Bradley,   Baylor College of Medicine
Strain of Origin		129S7/SvEvBrd-Hprt1+
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		Uox, urate oxidase
Chromosome		3
Gene Common Name(s)		AI663847; UOX-2; Uri; Uri2; expressed sequence AI663847;
Molecular Note		The insertion of a neomycin cassette into exon 3 disrupted the open reading frame at codon 107. Western blot analysis revealed an absence of encoded protein in liver extracts from homozygous mutant mice. Spectrographic analysis showing a lack of urate oxidase activity in liver extracts, confirmed functional ablation in homozygous mutant mice. [MGI Ref ID J:16490]

Genotyping

Genotyping Information

Genotyping Protocols

Uox^tm1Bay, STD PCR, vers. 2

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Wu X; Wakamiya M; Vaishnav S; Geske R; Montgomery C Jr; Jones P; Bradley A; Caskey CT. 1994. Hyperuricemia and urate nephropathy in urate oxidase-deficient mice. Proc Natl Acad Sci U S A 91(2):742-6. [PubMed: 8290593]  [MGI Ref ID J:16490]

Additional References

Uox^tm1Bay related

Kelly SJ; Delnomdedieu M; Oliverio MI; Williams LD; Saifer MG; Sherman MR; Coffman TM; Johnson GA; Hershfield MS. 2001. Diabetes insipidus in uricase-deficient mice: a model for evaluating therapy with poly(ethylene glycol)-modified uricase. J Am Soc Nephrol 12(5):1001-9. [PubMed: 11316859]  [MGI Ref ID J:103187]

Kunst CB; Messer L; Gordon J; Haines J; Patterson D. 2000. Genetic mapping of a mouse modifier gene that can prevent ALS onset Genomics 70(2):181-9. [PubMed: 11112346]  [MGI Ref ID J:66226]

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	When held in a live colony, this strain is maintained by homozygous sibling matings. The survival rate of homozygous mice can be improved with the administration of allopurinol. (Allopurinol therapy protocol)
Diet Information	LabDiet® 5K52/5K67

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

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. 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
	101045 B6129SF2/J	(approximate)
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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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

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

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

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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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