Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line Generation N10F35 (13-NOV-08)   Donating Investigator Nobuyo Maeda,   Univ of North Carolina at Chapel Hill

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Apoa1^tm1Unc targeted mutation have no APOA1 protein in their plasma. They have severely reduced levels of plasma cholesterol and HDL-cholesterol after overnight fasting. They also show a deficiency in alpha-migrating HDL particles. The Apoa1^tm1Unc mutant mice appear to develop normally.

Development
The Apoa1^tm1Unc mutant strain was developed in the laboratory of Dr. Nobuyo Maeda at the University of North Carolina at Chapel Hill. The 129-derived E14TG2a ES cell line was used. The C57BL/6J strain was produced by backcrossing the Apoa1^tm1Unc mutation 10 times to C57BL/6J inbred mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Apoa1^tm1Unc/Apoa1⁺

        B6.129P2-Apoa1^tm1Unc

• homeostasis/metabolism phenotype
• decreased circulating cholesterol level (MGI Ref ID J:22986)
  • plasma total cholesterol is 67% of wild-type

Apoa1^tm1Unc/Apoa1^tm1Unc

        B6.129P2-Apoa1^tm1Unc/J

• homeostasis/metabolism phenotype
• abnormal blood vessel healing (MGI Ref ID J:118063)
  • reendothelialization is delayed compared to in wild-type mice following injury to the carotid artery
  • mice exhibit a 52% larger area of non-reendothelialized carotid artery following injury compared to in wild-type mice
• decreased circulating cholesterol level (MGI Ref ID J:114205)
  • serum total cholesterol levels are reduced by one third compared to in wild-type mice
  • esterified cholesterol is reduced 7-fold and free cholesterol 1.6-fold compared to in wild-type mice
• decreased circulating HDL cholesterol level (MGI Ref ID J:114205)
  • Apoa1-poor HDL and Apoa1-rich HDL
• decreased circulating phospholipid level (MGI Ref ID J:114205)
  • serum phospholipids levels are reduced by one third compared to in wild-type mice
• increased circulating cholesterol level (MGI Ref ID J:114205)
  • serum total cholesterol, free cholesterol and esterified cholesterol levels in mice treated with silver nitrate to induce an acute phase response are increased more than in similarly treated wild-type mice
• increased circulating triglyceride level (MGI Ref ID J:114205)
  • triglyceride levels in mice treated with silver nitrate to induce an acute phase response are increased moderately compared to in similarly treated wild-type mice
• cardiovascular system phenotype
• abnormal blood vessel healing (MGI Ref ID J:118063)
  • reendothelialization is delayed compared to in wild-type mice following injury to the carotid artery
  • mice exhibit a 52% larger area of non-reendothelialized carotid artery following injury compared to in wild-type mice

Apoa1^tm1Unc/Apoa1^tm1Unc

        B6.129P2-Apoa1^tm1Unc

• homeostasis/metabolism phenotype
• decreased circulating cholesterol level (MGI Ref ID J:22986)
  • plasma total cholesterol is 25% of wild-type
  • plasma cholesteryl ester synthesis is reduced

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

Apoa1^tm1Unc/Apoa1⁺

        involves: 129P2/OlaHsd * C57BL/6J

• homeostasis/metabolism phenotype
• decreased circulating cholesterol level (MGI Ref ID J:2109)
  • at 8 weeks of age, total cholesterol levels are decreased to 54% of wild-type
• decreased circulating HDL cholesterol level (MGI Ref ID J:2109)
  • at 8 weeks of age, HDL levels are decreased to 40% of wild-type

Apoa1^tm1Unc/Apoa1^tm1Unc

        involves: 129P2/OlaHsd * C57BL/6J

• homeostasis/metabolism phenotype
• decreased circulating cholesterol level (MGI Ref ID J:2109)
  • at 8 weeks of age, total cholesterol levels are decreased to 33% of wild-type
• decreased circulating HDL cholesterol level (MGI Ref ID J:2109)
  • at 8 weeks of age, HDL levels are decreased to 17% of wild-type

Apoa1^tm1Unc/Apoa1^tm1Unc

        involves: 129P2/OlaHsd

• homeostasis/metabolism phenotype
• abnormal cellular cholesterol metabolism (MGI Ref ID J:120501)
  • HDL cholesteryl ether clearance is over 20-fold higher than in wild-type mice and varies depending on the organ examined
  • however, the clearance rate could be rescued by increasing plasma HDL cholesteryl ester levels
• decreased cholesterol efflux (MGI Ref ID J:129136)
• decreased circulating cholesterol level (MGI Ref ID J:129136)
• decreased circulating HDL cholesterol level (MGI Ref ID J:129136)
• decreased circulating phospholipid level (MGI Ref ID J:129136)
• cellular phenotype
• abnormal cellular cholesterol metabolism (MGI Ref ID J:120501)
  • HDL cholesteryl ether clearance is over 20-fold higher than in wild-type mice and varies depending on the organ examined
  • however, the clearance rate could be rescued by increasing plasma HDL cholesteryl ester levels
• decreased cholesterol efflux (MGI Ref ID J:129136)

View Research Applications

Research Applications

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

Apoa1^tm1Unc related

Cardiovascular Research
Hypocholesterolemia

Mouse/Human Gene Homologs
apolipoprotein A1 deficiency, amyloid polyneuropathy-nephropathy

Genes & Alleles

Gene & Allele Information

Allele Symbol		Apoa1tm1Unc
Allele Name		targeted mutation 1, University of North Carolina
Allele Type		Targeted (knock-out)
Common Name(s)		A1-; Apo A-1 KO; Apo A1<->; ApoA-I-; apoa1tm1unc;
Mutation Made By		Nobuyo Maeda,   Univ of North Carolina at Chapel Hill
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14TG2a
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Apoa1, apolipoprotein A-I
Chromosome		9
Gene Common Name(s)		Alp-1; Apoa-1; Brp-14; Ltw-1; Lvtw-1; MGC117399; Sep-1; Sep-2; Sep2; apoA-I; brain protein 14; liver 20-30 thousand M.Wt protein 1; serum protein 1; serum protein 2;
Molecular Note		A genomic fragment containing exon 2 was replaced by a neomycin resistance cassette. The protein was not detectable in plasma by Ouchterlony double-immunodiffusion tests in homozygous mice. [MGI Ref ID J:2109]

Genotyping

Genotyping Information

Genotyping Protocols

Apoa1^tm1Unc, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Williamson R; Lee D; Hagaman J; Maeda N. 1992. Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. Proc Natl Acad Sci U S A 89(15):7134-8. [PubMed: 1496008]  [MGI Ref ID J:2109]

Additional References

Ishiguro H; Yoshida H; Major AS; Zhu T; Babaev VR; Linton MF; Fazio S. 2001. Retrovirus-mediated expression of apolipoprotein A-I in the macrophage protects against atherosclerosis in vivo. J Biol Chem 276(39):36742-8. [PubMed: 11477092]  [MGI Ref ID J:71811]

Miettinen HE; Rayburn H; Krieger M. 2001. Abnormal lipoprotein metabolism and reversible female infertility in HDL receptor (SR-BI)-deficient mice. J Clin Invest 108(11):1717-22. [PubMed: 11733567]  [MGI Ref ID J:73138]

Parks JS; Li H; Gebre AK; Smith TL; Maeda N. 1995. Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma. J Lipid Res 36(2):349-55. [PubMed: 7751823]  [MGI Ref ID J:22986]

Apoa1^tm1Unc related

Alam K; Meidell RS; Spady DK. 2001. Effect of up-regulating individual steps in the reverse cholesterol transport pathway on reverse cholesterol transport in normolipidemic mice. J Biol Chem 276(19):15641-9. [PubMed: 11278646]  [MGI Ref ID J:69417]

Boisvert WA; Black AS; Curtiss LK. 1999. ApoA1 reduces free cholesterol accumulation in atherosclerotic lesions of ApoE-deficient mice transplanted with ApoE-expressing macrophages. Arterioscler Thromb Vasc Biol 19(3):525-30. [PubMed: 10073953]  [MGI Ref ID J:55595]

Cabana VG; Feng N; Reardon CA; Lukens J; Webb NR; de Beer FC; Getz GS. 2004. Influence of apoA-I and apoE on the formation of serum amyloid A-containing lipoproteins in vivo and in vitro. J Lipid Res 45(2):317-25. [PubMed: 14595002]  [MGI Ref ID J:121045]

Cabana VG; Reardon CA; Wei B; Lukens JR; Getz GS. 1999. SAA-only HDL formed during the acute phase response in apoA-I+/+ and apoA-I-/- mice. J Lipid Res 40(6):1090-103. [PubMed: 10357841]  [MGI Ref ID J:55744]

Callow MJ; Dudoit S; Gong EL; Speed TP; Rubin EM. 2000. Microarray expression profiling identifies genes with altered expression in HDL-deficient mice. Genome Res 10(12):2022-9. [PubMed: 11116096]  [MGI Ref ID J:115384]

Chiesa G; Parolini C; Canavesi M; Colombo N; Sirtori CR; Fumagalli R; Franceschini G; Bernini F. 1998. Human apolipoproteins A-I and A-II in cell cholesterol efflux: studies with transgenic mice. Arterioscler Thromb Vasc Biol 18(9):1417-23. [PubMed: 9743230]  [MGI Ref ID J:129136]

Chroni A; Duka A; Kan HY; Liu T; Zannis VI. 2005. Point mutations in apolipoprotein A-I mimic the phenotype observed in patients with classical lecithin:cholesterol acyltransferase deficiency. Biochemistry 44(43):14353-66. [PubMed: 16245952]  [MGI Ref ID J:105606]

Combes V; Coltel N; Alibert M; van Eck M; Raymond C; Juhan-Vague I; Grau GE; Chimini G. 2005. ABCA1 gene deletion protects against cerebral malaria: potential pathogenic role of microparticles in neuropathology. Am J Pathol 166(1):295-302. [PubMed: 15632021]  [MGI Ref ID J:95235]

Fagan AM; Christopher E; Taylor JW; Parsadanian M; Spinner M; Watson M; Fryer JD; Wahrle S; Bales KR; Paul SM; Holtzman DM. 2004. ApoAI deficiency results in marked reductions in plasma cholesterol but no alterations in amyloid-beta pathology in a mouse model of Alzheimer's disease-like cerebral amyloidosis. Am J Pathol 165(4):1413-22. [PubMed: 15466405]  [MGI Ref ID J:93658]

Goodrum JF; Bouldin TW; Zhang SH; Maeda N; Popko B. 1995. Nerve regeneration and cholesterol reutilization occur in the absence of apolipoproteins E and A-I in mice. J Neurochem 64(1):408-16. [PubMed: 7798939]  [MGI Ref ID J:22362]

Gruen ML; Plummer MR; Zhang W; Posey KA; Linton M; Fazio S; Hasty AH. 2005. Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. J Lipid Res 46(9):2007-14. [PubMed: 15995171]  [MGI Ref ID J:100492]

Hajri T; Elliott-Bryant R; Sipe JD; Liang JS; Hayes KC; Cathcart ES. 1998. The acute phase response in apolipoprotein A-1 knockout mice: apolipoprotein serum amyloid A and lipid distribution in plasma high density lipoproteins. Biochim Biophys Acta 1394(2-3):209-18. [PubMed: 9795222]  [MGI Ref ID J:114205]

Hirsch-Reinshagen V; Zhou S; Burgess BL; Bernier L; McIsaac SA; Chan JY; Tansley GH; Cohn JS; Hayden MR; Wellington CL. 2004. Deficiency of ABCA1 impairs apolipoprotein E metabolism in brain. J Biol Chem 279(39):41197-207. [PubMed: 15269218]  [MGI Ref ID J:93331]

Hopkins PC; Huang Y; McGuire JG; Pitas RE. 2002. Evidence for differential effects of apoE3 and apoE4 on HDL metabolism. J Lipid Res 43(11):1881-9. [PubMed: 12401887]  [MGI Ref ID J:123999]

Hughes SD; Verstuyft J; Rubin EM. 1997. HDL deficiency in genetically engineered mice requires elevated LDL to accelerate atherogenesis. Arterioscler Thromb Vasc Biol 17(9):1725-9. [PubMed: 9327769]  [MGI Ref ID J:43915]

Iqbal J; Hussain MM. 2005. Evidence for multiple complementary pathways for efficient cholesterol absorption in mice. J Lipid Res 46(7):1491-501. [PubMed: 15834127]  [MGI Ref ID J:100497]

Ishii T; Hasegawa T; Pai CI; Yvgi-Ohana N; Timberg R; Zhao L; Majdic G; Chung BC; Orly J; Parker KL. 2002. The roles of circulating high-density lipoproteins and trophic hormones in the phenotype of knockout mice lacking the steroidogenic acute regulatory protein. Mol Endocrinol 16(10):2297-309. [PubMed: 12351695]  [MGI Ref ID J:79229]

Ji Y; Wang N; Ramakrishnan R; Sehayek E; Huszar D; Breslow JL; Tall AR. 1999. Hepatic scavenger receptor BI promotes rapid clearance of high density lipoprotein free cholesterol and its transport into bile. J Biol Chem 274(47):33398-402. [PubMed: 10559220]  [MGI Ref ID J:115122]

Jolley CD; Dietschy JM; Turley SD. 2000. Induction of bile acid synthesis by cholesterol and cholestyramine feeding is unimpaired in mice deficient in apolipoprotein AI. Hepatology 32(6):1309-16. [PubMed: 11093738]  [MGI Ref ID J:87499]

Kypreos KE; Zannis VI. 2007. Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the participation of ABCA1 and LCAT. Biochem J 403(2):359-67. [PubMed: 17206937]  [MGI Ref ID J:121679]

Lee M; Calabresi L; Chiesa G; Franceschini G; Kovanen PT. 2002. Mast cell chymase degrades apoE and apoA-II in apoA-I-knockout mouse plasma and reduces its ability to promote cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 22(9):1475-81. [PubMed: 12231569]  [MGI Ref ID J:102936]

Li H; Reddick RL; Maeda N. 1993. Lack of apoA-I is not associated with increased susceptibility to atherosclerosis in mice. Arterioscler Thromb 13(12):1814-21. [PubMed: 8241102]  [MGI Ref ID J:28517]

Major AS; Dove DE; Ishiguro H; Su YR; Brown AM; Liu L; Carter KJ; Linton MF; Fazio S. 2001. Increased cholesterol efflux in apolipoprotein AI (ApoAI)-producing macrophages as a mechanism for reduced atherosclerosis in ApoAI((-/-)) mice. Arterioscler Thromb Vasc Biol 21(11):1790-5. [PubMed: 11701467]  [MGI Ref ID J:107390]

Moore RE; Navab M; Millar JS; Zimetti F; Hama S; Rothblat GH; Rader DJ. 2005. Increased atherosclerosis in mice lacking apolipoprotein A-I attributable to both impaired reverse cholesterol transport and increased inflammation. Circ Res 97(8):763-71. [PubMed: 16151025]  [MGI Ref ID J:114636]

Norata GD; Callegari E; Marchesi M; Chiesa G; Eriksson P; Catapano AL. 2005. High-density lipoproteins induce transforming growth factor-beta2 expression in endothelial cells. Circulation 111(21):2805-11. [PubMed: 15911702]  [MGI Ref ID J:112255]

Parks JS; Li H; Gebre AK; Smith TL; Maeda N. 1995. Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma. J Lipid Res 36(2):349-55. [PubMed: 7751823]  [MGI Ref ID J:22986]

Quan G; Xie C; Dietschy JM; Turley SD. 2003. Ontogenesis and regulation of cholesterol metabolism in the central nervous system of the mouse. Brain Res Dev Brain Res 146(1-2):87-98. [PubMed: 14643015]  [MGI Ref ID J:86935]

Seetharam D; Mineo C; Gormley AK; Gibson LL; Vongpatanasin W; Chambliss KL; Hahner LD; Cummings ML; Kitchens RL; Marcel YL; Rader DJ; Shaul PW. 2006. High-density lipoprotein promotes endothelial cell migration and reendothelialization via scavenger receptor-B type I. Circ Res 98(1):63-72. [PubMed: 16339487]  [MGI Ref ID J:118063]

Sorci-Thomas MG; Thomas M; Curtiss L; Landrum M. 2000. Single repeat deletion in ApoA-I blocks cholesterol esterification and results in rapid catabolism of delta6 and wild-type ApoA-I in transgenic mice. J Biol Chem 275(16):12156-63. [PubMed: 10766851]  [MGI Ref ID J:61733]

Spady DK; Woollett LA; Meidell RS; Hobbs HH. 1998. Kinetic characteristics and regulation of HDL cholesteryl ester and apolipoprotein transport in the apoA-I-/- mouse. J Lipid Res 39(7):1483-92. [PubMed: 9684752]  [MGI Ref ID J:120501]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Webb NR; de Beer MC; Asztalos BF; Whitaker N; van der Westhuyzen DR; de Beer FC. 2004. Remodeling of HDL remnants generated by scavenger receptor class B type I. J Lipid Res 45(9):1666-73. [PubMed: 15210842]  [MGI Ref ID J:93254]

Webb NR; de Beer MC; van der Westhuyzen DR; Kindy MS; Banka CL; Tsukamoto K; Rader DL; de Beer FC. 1997. Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice. J Lipid Res 38(8):1583-90. [PubMed: 9300780]  [MGI Ref ID J:42632]

Zabalawi M; Bharadwaj M; Horton H; Cline M; Willingham M; Thomas MJ; Sorci-Thomas MG. 2007. Inflammation and skin cholesterol in LDLr-/-, apoA-I-/- mice: link between cholesterol homeostasis and self-tolerance? J Lipid Res 48(1):52-65. [PubMed: 17071966]  [MGI Ref ID J:117480]

Zabalawi M; Bhat S; Loughlin T; Thomas MJ; Alexander E; Cline M; Bullock B; Willingham M; Sorci-Thomas MG. 2003. Induction of fatal inflammation in LDL receptor and ApoA-I double-knockout mice fed dietary fat and cholesterol. Am J Pathol 163(3):1201-13. [PubMed: 12937162]  [MGI Ref ID J:85174]

de Beer MC; van der Westhuyzen DR; Whitaker NL; Webb NR; de Beer FC. 2005. SR-BI-mediated selective lipid uptake segregates apoA-I and apoA-II catabolism. J Lipid Res 46(10):2143-50. [PubMed: 16061955]  [MGI Ref ID J:104721]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	This Apoa1tm1Unc strain is maintained by homozygous sibling matings. Homozygous mice may be ordered. Expected coat color from breeding:Black
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. 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
	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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Tel: 800.422.6423 or 207.288.5845
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Terms of Use

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Contact information

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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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