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/6J Donor Strain 129P2 via E14TG2a ES cell line Generation N13   Donating Investigator Oliver Smithies,   University of North Carolina

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Ace^tm1Unc 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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ace^tm1Unc/Ace⁺

        B6.129P2-Ace^tm1Unc

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

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

Ace^tm1Unc/Ace⁺

        involves: 129P2/OlaHsd * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:25284)
  • 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
• cardiovascular system phenotype
• hypotension (MGI Ref ID J:25284)
  • blood pressure is reduced by 15-20 mm Hg in males; females display normal blood pressure
• digestive/alimentary phenotype
• increased insulin secretion (MGI Ref ID J:128859)
  • compared to in Ace^tm3Unc heterozygotes when fed a high fat diet
• growth/size phenotype
• increased body weight (MGI Ref ID J:128859)
  • compared to in Ace^tm3Unc heterozygotes when fed a high fat diet
• adipose tissue phenotype
• abnormal epididymal fat pad morphology (MGI Ref ID J:128859)
  • when fed a high fat diet, peri-epididymal adipose tissue is increased compared to in Ace^tm3Unc heterozygotes
• reproductive system phenotype
• *normal* reproductive system phenotype (MGI Ref ID J:46177)
  • 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
• endocrine/exocrine gland phenotype
• increased insulin secretion (MGI Ref ID J:128859)
  • compared to in Ace^tm3Unc heterozygotes when fed a high fat diet

Ace^tm1Unc/Ace⁺

        involves: 129P2/OlaHsd

• cardiovascular system phenotype
• increased heart rate (MGI Ref ID J:42519)
• increased heart weight (MGI Ref ID J:42519)

Ace^tm1Unc/Ace^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• lethality-postnatal
• postnatal lethality (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
  • intercrossing of heterozygotes results in about 11% homozygous mutant mice compared with the expected 25%; the cause of this deviation has not been determined
• reproductive system phenotype
• abnormal male reproductive system physiology (MGI Ref ID J:46177)
  • mutant sperm show no significant differences in assays of viability, motility, capacitation, and induction of the acrosome reaction relative to wild-type sperm
  • 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
• reduced male fertility (MGI Ref ID J:25284)
  • 80% (4 of 5) males are unable to sire offspring
  • reduced fertility putatively due to an impaired ability to fertilize ova
  • normal testes morphology, normal spermatogenesis, and normal sperm count and morphology
  • females are fertile
• decreased litter size (MGI Ref ID J:25284)
  • 2 pups in a single litter
• impaired fertilization (MGI Ref ID J:46177)
  • 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
  • mutant sperm show defects in transport within the oviducts and in binding to zonae pellucidae
  • even those mutant sperm that reach the oviductal ampulla are less likely to fertilize eggs because of their reduced capacity for zona binding
• cardiovascular system phenotype
• abnormal kidney vasculature (MGI Ref ID J:25284)
  • intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen
• hypotension (MGI Ref ID J:25284)
  • blood pressure is reduced by ~35 mm Hg in both males and females
• renal/urinary system phenotype
• abnormal kidney cortex (MGI Ref ID J:25284)
  • cortical thinning
• abnormal kidney vasculature (MGI Ref ID J:25284)
  • intrarenal arteries display significant mural hypercellularity and thickening with narrowing of the lumen
• abnormal renal glomerulus morphology (MGI Ref ID J:25284)
  • crowding of glomeruli
• abnormal renal tubule morphology (MGI Ref ID J:25284)
  • shrinkage of tubules associated with a wedge-shaped zone of cortical atrophy in the subcapsular renal cortex
• kidney atrophy (MGI Ref ID J:25284)
  • focal areas of cortical atrophy
• kidney inflammation (MGI Ref ID J:25284)
  • chronic inflammation
• immune system phenotype
• kidney inflammation (MGI Ref ID J:25284)
  • chronic inflammation

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

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 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		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 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

Ace^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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]

Ace^tm1Unc 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]

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]

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

Colony Maintenance

Breeding & Husbandry	This 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
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.

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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

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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.

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.