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 Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line   Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Newborn homozygotes for the targeted disruption of Agt have no obvious pathological defects although only a few survive to adulthood. There are pathological changes in adult kidney and blood vessels. The effect of gene copy number was examined using these mice and C57BL/6J-TgH(Agtdup)1Unc (002690). Plasma angiotensinogen levels increase progressively, although not linearly, from zero in zero-copy (Agt^tm1Unc/Agt^tm1Unc) mice to 145% of normal in four-copy (Agt^dup/Agt^dup) mice. Mice of all genotypes are normal at birth, but most zero-copy animals show pathological changes as adults, the kidneys are normal in the other genotypes. The blood pressures of the one-copy through four-copy animals show significant and almost linear increases of approximately 8mmHg per gene copy despite their normal compensatory mechanisms being intact.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Agt

002690

B6.129P2-Agttm2Unc/J

View Strains carrying other alleles of Agt     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Agt^tm1Unc/Agt⁺

        involves: 129P2/OlaHsd * C57BL/6J

• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:24156)
  • have 35% of the level of angiotensinogen seen in wild-type
• increased circulating renin level (MGI Ref ID J:24156)
  • renin levels are 250% of normal levels
• cardiovascular system phenotype
• decreased blood pressure (MGI Ref ID J:24156)
• increased renal plasma flow rate (MGI Ref ID J:24156)
• renal/urinary system phenotype
• *normal* renal/urinary system phenotype (MGI Ref ID J:24156)
  • kidneys and glomerular filtration rate are normal
• increased renal plasma flow rate (MGI Ref ID J:24156)
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:24156)
  • do not exhibit a defect in ovulatory capacity is response to superovulation

Agt^tm1Unc/Agt^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:24156)
  • postnatal survival is severely compromised, however a few survive to adulthood
• homeostasis/metabolism phenotype
• abnormal blood chemistry (MGI Ref ID J:24156)
  • have no detectable levels of angiotensinogen
• cardiovascular system phenotype
• abnormal kidney vasculature (MGI Ref ID J:24156)
  • kidney vessels exhibit thickened walls caused by increased numbers of cells, which appear disorganized
  • defects are most pronounced in interlobular arteries
• decreased blood pressure (MGI Ref ID J:24156)
• renal/urinary system phenotype
• abnormal kidney cortex (MGI Ref ID J:24156)
  • generalized cortical thinning with focal areas of severe atrophy
• abnormal kidney vasculature (MGI Ref ID J:24156)
  • kidney vessels exhibit thickened walls caused by increased numbers of cells, which appear disorganized
  • defects are most pronounced in interlobular arteries
• kidney atrophy (MGI Ref ID J:24156)
  • kidneys exhibit focal areas of severe atrophy
  • atrophied areas show shrinkage and loss of tubules, interstitial fibrosis, and interstitial infiltration of chronic inflammatory cells
• renal interstitial fibrosis (MGI Ref ID J:24156)

View Research Applications

Research Applications

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

Internal/Organ Research
Kidney Defects

Agt^tm1Unc related

Cardiovascular Research
Hypertension
Vascular Defects

Endocrine Deficiency Research
Kidney Defects
Vasculature Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Agttm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		AGT-;
Mutation Made By		Oliver Smithies,   University of North Carolina
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Agt, angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
Chromosome		8
Gene Common Name(s)		AI265500; ANHU; ANRT; Ang; AngII; Aogen; FLJ92595; FLJ97926; MGC105326; PAT; SERPINA8; expressed sequence AI265500;
General Note		Human AGT and renin genes can complement the effects of the mouse null mutation (J:39934).
Molecular Note		A genomic fragment within exon 2 that codes for 114 amino acids of the encoded protein was replaced with a neomycin selection cassette. Radioimmunoassay tests confirmed that no protein was detectable in plasma of homozygous mice. [MGI Ref ID J:24156]

Genotyping

Genotyping Information

Genotyping Protocols

Agt^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kim HS; Krege JH; Kluckman KD; Hagaman JR; Hodgin JB; Best CF; Jennette JC; Coffman TM; Maeda N; Smithies O. 1995. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci U S A 92(7):2735-9. [PubMed: 7708716]  [MGI Ref ID J:24156]

Additional References

Agt^tm1Unc related

Bozec E; Lacolley P; Bergaya S; Boutouyrie P; Meneton P; Herisse-Legrand M; Boulanger CM; Alhenc-Gelas F; Kim HS; Laurent S; Dabire H. 2004. Arterial stiffness and angiotensinogen gene in hypertensive patients and mutant mice. J Hypertens 22(7):1299-307. [PubMed: 15201545]  [MGI Ref ID J:105585]

Davisson RL; Kim HS; Krege JH; Lager DJ; Smithies O; Sigmund CD. 1997. Complementation of reduced survival, hypotension, and renal abnormalities in angiotensinogen-deficient mice by the human renin and human angiotensinogen genes. J Clin Invest 99(6):1258-64. [PubMed: 9077534]  [MGI Ref ID J:39934]

Ding Y; Stec DE; Sigmund CD. 2001. Genetic evidence that lethality in angiotensinogen-deficient mice is due to loss of systemic but not renal angiotensinogen. J Biol Chem 276(10):7431-6. [PubMed: 11096065]  [MGI Ref ID J:135051]

Fern RJ; Yesko CM; Thornhill BA; Kim HS; Smithies O; Chevalier RL. 1999. Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice. J Clin Invest 103(1):39-46. [PubMed: 9884332]  [MGI Ref ID J:51936]

Hefler LA; Gregg AR. 2001. Influence of the angiotensinogen gene on the ovulatory capacity of mice. Fertil Steril 75(6):1206-11. [PubMed: 11384650]  [MGI Ref ID J:69609]

Kim HS; Maeda N; Oh GT; Fernandez LG; Gomez RA; Smithies O. 1999. Homeostasis in mice with genetically decreased angiotensinogen is primarily by an increased number of renin-producing cells. J Biol Chem 274(20):14210-7. [PubMed: 10318840]  [MGI Ref ID J:55000]

Lochard N; Silversides DW; van Kats JP; Mercure C; Reudelhuber TL. 2003. Brain-specific restoration of angiotensin II corrects renal defects seen in angiotensinogen-deficient mice. J Biol Chem 278(4):2184-9. [PubMed: 12399452]  [MGI Ref ID J:81733]

Matsusaka T; Fogo A; Ichikawa I. 1997. Targeting the genes of angiotensin receptors. Semin Nephrol 17(5):396-403. [PubMed: 9316207]  [MGI Ref ID J:78469]

Smithies O; Kim HS. 1994. Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. Proc Natl Acad Sci U S A 91(9):3612-5. [PubMed: 8170956]  [MGI Ref ID J:18272]

Sun Z; Cade R; Zhang Z; Alouidor J; Van H. 2003. Angiotensinogen gene knockout delays and attenuates cold-induced hypertension. Hypertension 41(2):322-7. [PubMed: 12574102]  [MGI Ref ID J:102953]

Tempfer CB; Moreno RM; Gregg AR. 2000. Genetic control of fertility and embryonic waste in the mouse: A rolefor angiotensinogen. Biol Reprod 62(2):457-62. [PubMed: 10642587]  [MGI Ref ID J:59883]

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

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
	Wild-type from the colony
	000664 C57BL/6J
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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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

Contact information

General inquiries

Contracts Administration

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.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.