Strain Name:

B6.129P2-Acetm1Unc/J

Stock Number:

002679

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Availability:

Cryopreserved - Ready for recovery

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.
Specieslaboratory mouse
Background Strain C57BL/6J
Donor Strain 129P2 via E14TG2a ES cell line
 
Donating InvestigatorDr. Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Acetm1Unc targeted mutation lack both the somatic and testicular isozyme forms of the Ace gene. They show reduced viability prior to weaning. Surviving homozygotes are hypotensive with blood pressures ~35 mmHg lower than normal wildtype silbings. Heterozygous male mice have blood pressures 15-20 mmHg below wildtype siblings. Fertility of homozygous males is greatly impaired. Ten to twelve month old female homoygotes exhibit abnormal renal vessels and tubules, increased renin synthesis accompanied by an abnormal expression pattern.

Control Information

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

Related Strains

Strains carrying other alleles of Ace
002689   B6.129P2-Acetm3Unc/J
View Strains carrying other alleles of Ace     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Alzheimer Disease; AD   (ACE)
Angiotensin I-Converting Enzyme; ACE   (ACE)
Hemorrhage, Intracerebral, Susceptibility To; ICH   (ACE)
Microvascular Complications of Diabetes, Susceptibility to, 3; MVCD3   (ACE)
Renal Tubular Dysgenesis; RTD   (ACE)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Acetm1Unc/Ace+

        B6.129P2-Acetm1Unc
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • streptozotocin induces a diabetes phenotype indistinguishable from that observed in similarly treated wild-type mice   (MGI Ref ID J:72577)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Acetm1Unc/Ace+

        involves: 129P2/OlaHsd * C57BL/6J
  • mortality/aging
  • partial postnatal lethality
    • at weaning, the proportions of wild-type and heterozygous offspring differ significantly from the expected Mendelian ratios; the cause of this deviation has not been determined   (MGI Ref ID J:25284)
  • cardiovascular system phenotype
  • hypotension
    • blood pressure is reduced by 15-20 mm Hg in males; females display normal blood pressure   (MGI Ref ID J:25284)
  • growth/size/body phenotype
  • increased body weight
    • compared to in Acetm3Unc heterozygotes when fed a high fat diet   (MGI Ref ID J:128859)
  • adipose tissue phenotype
  • abnormal epididymal fat pad morphology
    • when fed a high fat diet, peri-epididymal adipose tissue is increased compared to in Acetm3Unc heterozygotes   (MGI Ref ID J:128859)
  • reproductive system phenotype
  • *normal* reproductive system phenotype
    • males heterozygotes sire wild type and heterozygous offspring at an indistinguishable frequency, indicating functionally intact sperm males heterozygotes sire wild-type and heterozygous offspring at an indistinguishable frequency, indicating functionally intact sperm   (MGI Ref ID J:46177)
  • endocrine/exocrine gland phenotype
  • increased insulin secretion
    • compared to in Acetm3Unc heterozygotes when fed a high fat diet   (MGI Ref ID J:128859)
  • homeostasis/metabolism phenotype
  • increased insulin secretion
    • compared to in Acetm3Unc heterozygotes when fed a high fat diet   (MGI Ref ID J:128859)

Acetm1Unc/Ace+

        involves: 129P2/OlaHsd
  • cardiovascular system phenotype
  • increased heart rate   (MGI Ref ID J:42519)
  • increased heart weight   (MGI Ref ID J:42519)

Acetm1Unc/Acetm1Unc

        involves: 129P2/OlaHsd * C57BL/6J
  • mortality/aging
  • partial postnatal lethality
    • intercrossing of heterozygotes results in about 11% homozygous mutant mice compared with the expected 25%; the cause of this deviation has not been determined   (MGI Ref ID J:25284)
    • at weaning, the proportions of wild-type, heterozygous and homozygous offspring differ significantly from the expected 1:2:1 Mendelian ratios   (MGI Ref ID J:25284)
  • reproductive system phenotype
  • abnormal male reproductive system physiology
    • mutant sperm show no significant differences in assays of viability, motility, capacitation, and induction of the acrosome reaction relative to wild-type sperm   (MGI Ref ID J:46177)
    • however, very few mutant sperm progress beyond the two oviduct regions nearest the uterus at 1 hr after mating, whereas significantly more wild-type sperm reach the extramural uterotubal junction and the lower and upper isthmus regions of the oviducts under identical conditions   (MGI Ref ID J:46177)
    • reduced male fertility
      • 80% (4 of 5) males are unable to sire offspring   (MGI Ref ID J:25284)
      • reduced fertility putatively due to an impaired ability to fertilize ova   (MGI Ref ID J:25284)
      • normal testes morphology, normal spermatogenesis, and normal sperm count and morphology   (MGI Ref ID J:25284)
      • females are fertile   (MGI Ref ID J:25284)
  • decreased litter size
    • 2 pups in a single litter   (MGI Ref ID J:25284)
  • impaired fertilization
    • sperm from male homozygotes achieve in vivo fertilization at a reduced frequency: >65% of eggs from wild-type matings become fertilized and develop to the 8-cell stage or beyond compared with <5% of eggs harvested from wild-type females inseminated by homozygous mutant males   (MGI Ref ID J:46177)
    • mutant sperm show defects in transport within the oviducts and in binding to zonae pellucidae   (MGI Ref ID J:46177)
    • even those mutant sperm that reach the oviductal ampulla are less likely to fertilize eggs because of their reduced capacity for zona binding   (MGI Ref ID J:46177)
  • cardiovascular system phenotype
  • abnormal kidney blood vessel morphology
    • intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen   (MGI Ref ID J:25284)
  • hypotension
    • blood pressure is reduced by ~35 mm Hg in both males and females   (MGI Ref ID J:25284)
  • renal/urinary system phenotype
  • abnormal kidney blood vessel morphology
    • intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen   (MGI Ref ID J:25284)
  • abnormal renal glomerulus morphology
    • crowding of glomeruli   (MGI Ref ID J:25284)
  • kidney cortex atrophy
    • focal areas of cortical thinning   (MGI Ref ID J:25284)
  • kidney inflammation
    • chronic inflammation   (MGI Ref ID J:25284)
  • renal tubule atrophy
    • shrinkage of tubules associated with a wedge-shaped zone of cortical atrophy in the subcapsular renal cortex   (MGI Ref ID J:25284)
  • immune system phenotype
  • kidney inflammation
    • chronic inflammation   (MGI Ref ID J:25284)
View Research Applications

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

Cardiovascular Research
Hypotension

Internal/Organ Research
Heart Abnormalities

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Acetm1Unc
Allele Name targeted mutation 1, University of North Carolina
Allele Type Targeted (knock-out)
Common Name(s) ACE-KO; stst;
Mutation Made ByDr. Oliver Smithies,   University of North Carolina
Strain of Origin129P2/OlaHsd
ES Cell Line NameE14TG2a
ES Cell Line Strain129P2/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; ICH; MVCD3; StsRR92; expressed sequence AW208573;
Molecular Note A neomycin selection cassette was inserted into exon 14 of the gene. Exon 14 encodes amino acids critical for the normal function of both isoforms of the protein. [MGI Ref ID J:25284]

Genotyping

Genotyping Information

Genotyping Protocols

Acetm1Unc, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Krege JH; John SW; Langenbach LL; Hodgin JB; Hagaman JR; Bachman ES; Jennette JC; O'Brien DA; Smithies O. 1995. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature 375(6527):146-8. [PubMed: 7753170]  [MGI Ref ID J:25284]

Additional References

Crackower MA; Sarao R; Oudit GY; Yagil C; Kozieradzki I; Scanga SE; Oliveira-dos-Santos AJ; da Costa J; Zhang L; Pei Y; Scholey J; Ferrario CM; Manoukian AS; Chappell MC; Backx PH; Yagil Y; Penninger JM. 2002. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417(6891):822-8. [PubMed: 12075344]  [MGI Ref ID J:77232]

Acetm1Unc related

Carlson SH; Oparil S; Chen YF; Wyss JM. 2002. Blood pressure and NaCl-sensitive hypertension are influenced by angiotensin-converting enzyme gene expression in transgenic mice. Hypertension 39(2):214-8. [PubMed: 11847186]  [MGI Ref ID J:103419]

Crackower MA; Sarao R; Oudit GY; Yagil C; Kozieradzki I; Scanga SE; Oliveira-dos-Santos AJ; da Costa J; Zhang L; Pei Y; Scholey J; Ferrario CM; Manoukian AS; Chappell MC; Backx PH; Yagil Y; Penninger JM. 2002. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417(6891):822-8. [PubMed: 12075344]  [MGI Ref ID J:77232]

Esther CR Jr; Howard TE; Marino EM; Goddard JM; Capecchi MR; Bernstein KE. 1996. Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility. Lab Invest 74(5):953-65. [PubMed: 8642790]  [MGI Ref ID J:33018]

Hagaman JR; Moyer JS; Bachman ES; Sibony M; Magyar PL; Welch JE; Smithies O; Krege JH; O'Brien DA. 1998. Angiotensin-converting enzyme and male fertility. Proc Natl Acad Sci U S A 95(5):2552-7. [PubMed: 9482924]  [MGI Ref ID J:46177]

Haxhija EQ; Yang H; Spencer AU; Koga H; Sun X; Teitelbaum DH. 2008. Modulation of mouse intestinal epithelial cell turnover in the absence of angiotensin converting enzyme. Am J Physiol Gastrointest Liver Physiol 295(1):G88-G98. [PubMed: 18483182]  [MGI Ref ID J:137525]

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]

Imai Y; Kuba K; Rao S; Huan Y; Guo F; Guan B; Yang P; Sarao R; Wada T; Leong-Poi H; Crackower MA; Fukamizu A; Hui CC; Hein L; Uhlig S; Slutsky AS; Jiang C; Penninger JM. 2005. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436(7047):112-6. [PubMed: 16001071]  [MGI Ref ID J:100334]

Jayasooriya AP; Mathai ML; Walker LL; Begg DP; Denton DA; Cameron-Smith D; Egan GF; McKinley MJ; Rodger PD; Sinclair AJ; Wark JD; Weisinger HS; Jois M; Weisinger RS. 2008. Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance. Proc Natl Acad Sci U S A 105(18):6531-6. [PubMed: 18443281]  [MGI Ref ID J:134642]

Kessler SP; Gomos JB; Scheidemantel TS; Rowe TM; Smith HL; Sen GC. 2002. The germinal isozyme of angiotensin-converting enzyme can substitute for the somatic isozyme in maintaining normal renal structure and functions. J Biol Chem 277(6):4271-6. [PubMed: 11723129]  [MGI Ref ID J:74527]

Kessler SP; Hashimoto S; Senanayake PS; Gaughan C; Sen GC; Schnermann J. 2005. Nephron function in transgenic mice with selective vascular or tubular expression of Angiotensin-converting enzyme. J Am Soc Nephrol 16(12):3535-42. [PubMed: 16221869]  [MGI Ref ID J:133982]

Kessler SP; Rowe TM; Gomos JB; Kessler PM; Sen GC. 2000. Physiological non-equivalence of the two isoforms of angiotensin-converting enzyme J Biol Chem 275(34):26259-64. [PubMed: 10831599]  [MGI Ref ID J:63999]

Kessler SP; Senanayake P; Gaughan C; Sen GC. 2007. Vascular expression of germinal ACE fails to maintain normal blood pressure in ACE-/- mice. FASEB J 21(1):156-66. [PubMed: 17135368]  [MGI Ref ID J:129753]

Kessler SP; deS Senanayake P; Scheidemantel TS; Gomos JB; Rowe TM; Sen GC. 2003. Maintenance of normal blood pressure and renal functions are independent effects of angiotensin-converting enzyme. J Biol Chem 278(23):21105-12. [PubMed: 12777443]  [MGI Ref ID J:83777]

Kondoh G; Tojo H; Nakatani Y; Komazawa N; Murata C; Yamagata K; Maeda Y; Kinoshita T; Okabe M; Taguchi R; Takeda J. 2005. Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization. Nat Med 11(2):160-166. [PubMed: 15665832]  [MGI Ref ID J:96051]

Lacchini S; Heimann AS; Evangelista FS; Cardoso L; Silva GJ; Krieger JE. 2009. Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice. Physiol Genomics 37(3):225-30. [PubMed: 19258495]  [MGI Ref ID J:157968]

Machura K; Steppan D; Neubauer B; Alenina N; Coffman TM; Facemire CS; Hilgers KF; Eckardt KU; Wagner C; Kurtz A. 2009. Developmental renin expression in mice with a defective renin-angiotensin system. Am J Physiol Renal Physiol 297(5):F1371-80. [PubMed: 19710239]  [MGI Ref ID J:153990]

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]

Nakanishi T; Isotani A; Yamaguchi R; Ikawa M; Baba T; Suarez SS; Okabe M. 2004. Selective passage through the uterotubal junction of sperm from a mixed population produced by chimeras of calmegin-knockout and wild-type male mice. Biol Reprod 71(3):959-65. [PubMed: 15151931]  [MGI Ref ID J:160202]

Oudit GY; Crackower MA; Backx PH; Penninger JM. 2003. The Role of ACE2 in Cardiovascular Physiology. Trends Cardiovasc Med 13(3):93-101. [PubMed: 12691672]  [MGI Ref ID J:83218]

Ramaraj P; Kessler SP; Colmenares C; Sen GC. 1998. Selective restoration of male fertility in mice lacking angiotensin-converting enzymes by sperm-specific expression of the testicular isozyme. J Clin Invest 102(2):371-8. [PubMed: 9664078]  [MGI Ref ID J:48697]

Schnermann J. 1999. Micropuncture analysis of tubuloglomerular feedback regulation in transgenic mice. J Am Soc Nephrol 10(12):2614-9. [PubMed: 10589702]  [MGI Ref ID J:59838]

Tian B; Meng QC; Chen YF; Krege JH; Smithies O; Oparil S. 1997. Blood pressures and cardiovascular homeostasis in mice having reduced or absent angiotensin-converting enzyme gene function. Hypertension 30(1 Pt 1):128-33. [PubMed: 9231832]  [MGI Ref ID J:42643]

Traynor T; Yang T; Huang YG; Krege JH; Briggs JP; Smithies O; Schnermann J. 1999. Tubuloglomerular feedback in ACE-deficient mice. Am J Physiol 276(5 Pt 2):F751-7. [PubMed: 10330057]  [MGI Ref ID J:56143]

Wei CC; Tian B; Perry G; Meng QC; Chen YF; Oparil S; Dell'Italia LJ. 2002. Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene. Am J Physiol Heart Circ Physiol 282(6):H2254-8. [PubMed: 12003835]  [MGI Ref ID J:83637]

Yamaguchi R; Yamagata K; Ikawa M; Moss SB; Okabe M. 2006. Aberrant Distribution of ADAM3 in Sperm from Both Angiotensin-Converting Enzyme (Ace)- and Calmegin (Clgn)-Deficient Mice. Biol Reprod 75(5):760-6. [PubMed: 16870943]  [MGI Ref ID J:114470]

van den Buuse M; Zheng TW; Walker LL; Denton DA. 2005. Angiotensin-converting enzyme (ACE) interacts with dopaminergic mechanisms in the brain to modulate prepulse inhibition in mice. Neurosci Lett 380(1-2):6-11. [PubMed: 15854741]  [MGI Ref ID J:104829]

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 was generated on a 129/Ola genetic background. As of 5/96 it had been backcrossed 8 times to C57BL/6J. It is maintained by breeding heterozygous males to C57BL/6J females. The Y chromosome in these males is therefore 129/Ola, ES cell-derived. 11/6/98: Contact Peter Schweitzer for typing information. Expected coat color from breeding:Black

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* $2450.00
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.

Standard Supply

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

Supply Notes

  • 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 11 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* $3185.00
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.

Standard Supply

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

Supply Notes

  • 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 11 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
   Wild-type from the colony
   000664 C57BL/6J
 
  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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