Description

Strain Information

Former Names B6.129P2-Tg(Acedup)2Unc/J    (Changed: 01-MAR-06 ) Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129P2 via E14TG2a ES cell line Generation N6F9   Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
The entire angiotensin converting gene is duplicated in this strain by homologous recombination (gap repair gene targeting). Mice that are heterozygous for this mutation have three functional genes. Mice that are homozygous for this mutation have four functional genes. This permits examination of the effects of having two (wildtype), three or four functional copies of the targeted gene in its normal chromosomal location. Serum ACE activities increased progressively from 62% in one copy mice to 144% of normal in three copy animals. Blood pressures did not differ significantly; however, heart rates, heart weights and renal tubulointerstitial volumes decreased significantly with increasing copy number. This mutant mouse strain may be useful in studies of cardiovascular and renal disease.

Development
This allele was made in the laboratory of Dr. Oliver Smithies at the University of North Carolina,Chapel Hill. Duplication of the targeted gene was generated by a special form of gap-repair targeting that tandemly duplicates the whole of a gene together with the 5' and 3' flanking regions. The targeting vector, containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to insert two copies of the gene, separated by the neomycin resistance gene, into the endogenous locus. The construct was electroporated into 129P2/OlaHsd derived E14TG2a (BK4 subline) embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animal was crossed to C57BL/6J female mice, and then backcrossed to the same for 6 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ace

002679

B6.129P2-Acetm1Unc/J

View Strains carrying other alleles of Ace     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ace^tm3Unc/Ace⁺

        B6.129P2-Ace^tm3Unc

• homeostasis/metabolism phenotype
• albuminuria (MGI Ref ID J:72577)
  • in streptozotocin-induced diabetic, urinary albumin is nearly doubled compared to similarly treated wild-type mice and continues to increase with age
  • however, mice fail to exhibit evidence of structural renal injury
• cardiovascular system phenotype
• increased blood pressure (MGI Ref ID J:72577)
  • in streptozotocin-induced diabetic mice
• renal/urinary system phenotype
• albuminuria (MGI Ref ID J:72577)
  • in streptozotocin-induced diabetic, urinary albumin is nearly doubled compared to similarly treated wild-type mice and continues to increase with age
  • however, mice fail to exhibit evidence of structural renal injury

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

Ace^tm3Unc/Ace⁺

        involves: 129P2/OlaHsd * C57BL/6J

• growth/size phenotype
• decreased body weight (MGI Ref ID J:128859)
  • based on weight normalized by food consumption, mice are thinner than wild-type mice
  • when fed a high fat diet for 27 weeks, mice weigh less than wild-type mice and Ace^tm1Unc heterozygotes
  • decreased weight when fed a high fat diet cannot be reversed with treatment with losartan (an angiotensin AT1 antagonist)
• renal/urinary system phenotype
• abnormal kidney cortex (MGI Ref ID J:42519)
  • cortical width is decreased compared to wild-type
• abnormal renal glomerulus morphology (MGI Ref ID J:42519)
  • mice exhibit decreased tubulointerstitial tissue per glomerulus compared to in wild-type mice
• cardiovascular system phenotype
• decreased heart rate (MGI Ref ID J:42519)
• decreased heart weight (MGI Ref ID J:42519)
• adipose tissue phenotype
• abnormal epididymal fat pad morphology (MGI Ref ID J:128859)
  • when fed a high fat diet, peri-epididymal adipose tissue is reduced
• behavior/neurological phenotype
• increased eating behavior (MGI Ref ID J:128859)
  • food consumption is increased on a normal diet in order to maintain a normal body weight
• digestive/alimentary phenotype
• decreased insulin secretion (MGI Ref ID J:128859)
  • compared to in Ace^tm1Unc heterozygotes when fed a high fat diet
• endocrine/exocrine gland phenotype
• decreased insulin secretion (MGI Ref ID J:128859)
  • compared to in Ace^tm1Unc heterozygotes when fed a high fat diet

Ace^tm3Unc/Ace^tm3Unc

        involves: 129P2/OlaHsd * C57BL/6J

• cardiovascular system phenotype
• decreased heart rate (MGI Ref ID J:42519)
  • mice exhibit a lower heart rate than in wild-type and heterozygous mice
• decreased heart weight (MGI Ref ID J:42519)
  • mice exhibit a lower heart weight than in wild-type mice but is not different from heart weights in heterozygous mice
• renal/urinary system phenotype
• abnormal kidney cortex (MGI Ref ID J:42519)
  • cortical width is decreased compared to wild-type and heterogyzous mice
• abnormal renal glomerulus morphology (MGI Ref ID J:42519)
  • mice exhibit decreased tubulointerstitial tissue per glomerulus compared to wild-type and heterogyzous mice

View Research Applications

Research Applications

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

Cardiovascular Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information

Allele Symbol		Acetm3Unc
Allele Name		targeted mutation 3, University of North Carolina
Allele Type		Targeted (knock-in)
Common Name(s)		Tg(Acedup)2Unc; TgH(Acedup)2Unc;
Mutation Made By		Oliver Smithies,   University of North Carolina
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		BK4
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Ace, angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
Chromosome		11
Gene Common Name(s)		ACE1; AW208573; CD143; DCP; DCP1; MGC26566; StsRR92; expressed sequence AW208573;
Molecular Note		A gap-repair type targeting vector was used to induce a gene duplication. Two tandem copies of the gene were present in the final allele. Protein activity measurments correlated with gene dosage in serum and lung tissue. [MGI Ref ID J:42519]

Genotyping

Genotyping Information

Genotyping Protocols

Ace^tm3Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Krege JH; Kim HS; Moyer JS; Jennette JC; Peng L; Hiller SK; Smithies O. 1997. Angiotensin-converting enzyme gene mutations, blood pressures, and cardiovascular homeostasis. Hypertension 29(1 Pt 2):150-7. [PubMed: 9039095]  [MGI Ref ID J:42519]

Additional References

Ace^tm3Unc related

Heimann AS; Favarato MH; Gozzo FC; Rioli V; Carreno FR; Eberlin MN; Ferro ES; Krege JH; Krieger JE. 2005. ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight. Physiol Genomics 20(2):173-82. [PubMed: 15522949]  [MGI Ref ID J:128859]

Huang W; Gallois Y; Bouby N; Bruneval P; Heudes D; Belair MF; Krege JH; Meneton P; Marre M; Smithies O; Alhenc-Gelas F. 2001. Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci U S A 98(23):13330-4. [PubMed: 11687636]  [MGI Ref ID J:72577]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, this strain is maintained by homozygous sibling matings. Expected coat color from breeding:Black

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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.

Control Information

	Control
	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.

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Ordering and Purchasing Information

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Contact Information
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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.

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