Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation ?+F3 (03-DEC-07)   Donating Investigator Jan Breslow,   Rockefeller University

Description
Mice homozygous for this targeted mutation are viable and fertile with no protein detectable in plasma, liver, or intestinal tissues. Homozygotes have decreased plasma levels of cholesterol, free fatty acids, and high density (HDL) and very low density lipoprotein (VLDL). These mice may be useful in studies of lipid metabolism, atherosclerosis, heart disease, appetite regulation, intestinal lipid absorption, or inflammatory bowel disease.

Development
A targeting vector was designed to replace exon 1 of the endogenous gene with a neomycin resistance gene. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric mice were bred with C57BL/6J and the resulting heterozygous offspring were bred together for many generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

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.

Apoa4^tm1Bres/Apoa4^tm1Bres

        either: 129 or (involves: 129 * C57BL/6)

• homeostasis/metabolism phenotype
• abnormal lipid homeostasis (MGI Ref ID J:43015)
  • decreased triglyceride transport rate
• abnormal cholesterol homeostasis (MGI Ref ID J:43015)
  • 27% increase in the HDL-cholesterol ester catabolic rate
• decreased circulating cholesterol level (MGI Ref ID J:43015)
  • reduced 23% in both fed and fasted state
• decreased circulating HDL cholesterol level (MGI Ref ID J:43015)
  • reduced 23%
• decreased circulating triglyceride level (MGI Ref ID J:43015)
  • reduced 45%
  • levels are tied more to Apoa3 levels (which are also reduced) than to Apoa4 levels
• decreased circulating VLDL triglyceride level (MGI Ref ID J:43015)
  • reduced 61%
• behavior/neurological phenotype
• abnormal eating behavior (MGI Ref ID J:43015)
  • animals fasted 18 hours before being given unlimited food had higher short term food intake than controls but the difference is only significant on a predominantly 129 background

Apoa4^tm1Bres/Apoa4^tm1Bres

        B6.129-Apoa4^tm1Bres

• digestive/alimentary phenotype
• increased susceptibility to induced colitis (MGI Ref ID J:91357)
  • increased severity of colitis experimentally induced by providing sodium dextran sulfate in the drinking water
• immune system phenotype
• increased susceptibility to induced colitis (MGI Ref ID J:91357)
  • increased severity of colitis experimentally induced by providing sodium dextran sulfate in the drinking water

View Research Applications

Research Applications

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

Cardiovascular Research
Atherosclerosis
Hypocholesterolemia
Other (altered fat metabolism)
Other (altered lipoprotein profile)

Diabetes and Obesity Research
Hypoinsulinemia
Insulin Resistance

Internal/Organ Research
Gastrointestinal Defects (colitis)

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Apoa4tm1Bres
Allele Name		targeted mutation 1, Jan L Breslow
Allele Type		Targeted (knock-out)
Common Name(s)		apoA-IV -;
Mutation Made By		Jan Breslow,   Rockefeller University
Strain of Origin		129
ES Cell Line Strain		129
Gene Symbol and Name		Apoa4, apolipoprotein A-IV
Chromosome		9
Gene Common Name(s)		Apoa-4; MGC142154; MGC142156;
Molecular Note		A 1.1kb genomic fragment containing exon 1 and intron 1 was replaced with a neomycin selection cassette. No transcript was detectable in northern blot analysis on intestinal RNA from homozygous mice, and western blot analysis demonstrated that no stableprotein was detectable in plasma of homozygous mice. [MGI Ref ID J:43015]

Genotyping

Genotyping Information

Genotyping Protocols

Apoa4^tm1Bres, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Weinstock PH; Bisgaier CL; Hayek T; Aalto-Setala K; Sehayek E ; Wu L ; Sheiffele P ; Merkel M ; Essenburg AD ; Breslow JL. 1997. Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice. J Lipid Res 38(9):1782-94. [PubMed: 9323588]  [MGI Ref ID J:43015]

Additional References

Apoa4^tm1Bres related

Vowinkel T; Mori M; Krieglstein CF; Russell J; Saijo F; Bharwani S; Turnage RH; Davidson WS; Tso P; Granger DN; Kalogeris TJ. 2004. Apolipoprotein A-IV inhibits experimental colitis. J Clin Invest 114(2):260-9. [PubMed: 15254593]  [MGI Ref ID J:91357]

Whited KL; Tso P; Raybould HE. 2007. Involvement of apolipoprotein A-IV and cholecystokinin1 receptors in exogenous peptide YY3 36-induced stimulation of intestinal feedback. Endocrinology 148(10):4695-703. [PubMed: 17641001]  [MGI Ref ID J:129467]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice are bred together.
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.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
	101045 B6129SF2/J	(approximate)
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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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.