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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+F1p   Donating Investigator Thomas Sudhof,   Stanford University School of Medicine

Description
Triple homozygous knock-in mice are viable and fertile and and do not display any gross physical or behavioral abnormalities. Expression of all three proteins is normal. When crossed with a cre deleter strain that eradicates protein expression, Apba1/Abcba2 (Apba1/2) double knockout and Apba1/2/3 triple knockout mice exhibit a high percentage of postnatal lethality (only ~20% of the mice survive). Apba1/2 mice are visually indistinguishable from their littermates and display no major alterations in breathing, movements or reaction to stimuli several hours after birth, but fail to nurse and die within 24 hours. Their brains are morphologically and structurally normal. Quantitation of 18 neuronal proteins fails to reveal significant changes. Surviving mice show reduced weight gain and exhibit movement dysfunction. Cultured neurons from triple knock-in neonates show impairments in presynaptic neurotransmitter release after treatment with lentiviral cre. Apba1/3 and Apba2/3 double knockouts created from crosses with a cre deleter strain survive normally.

Development
loxP sites flanking the first coding exon of Apba1, residues 368-416 of the Apba2, and exon 3 of Apba3 (encoding residues 201-249) were incorporated into three targeting vectors which also contained Frt-flanked neomycin resistance cassettes inserted into the respective downstream (Apba1 and Apba2) or upstream (Apba3) introns. The constructs were independently electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. The neomycin cassettes were subsequently excised from all but the Apba1 mutant strain in which the drug selection cassette does not interfere with expression. Compound mutant mice were generated by intercrossing the individual mutant lines.

Control Information

	Control
	None Available
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Neurobiology Research
Alzheimer's Disease

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information

Allele Symbol		Apba1tm1Sud
Allele Name		targeted mutation 1, Thomas C Sudhof
Allele Type		Targeted (Floxed/Frt)
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Apba1, amyloid beta (A4) precursor protein binding, family A, member 1
Chromosome		19
Gene Common Name(s)		6430513E09Rik; D9S411E; Lin-10; MINT1; Mint; RIKEN cDNA 6430513E09 gene; X11; X11A; X11ALPHA;
Molecular Note		Flanking loxP sites were introduced to exon 1 and an frt-flanked neomycin resistance cassette was inserted into the downstream intron via homologous recombination. [MGI Ref ID J:81845]
Allele Symbol		Apba2tm1Sud
Allele Name		targeted mutation 1, Thomas C Sudhof
Allele Type		Targeted (Floxed/Frt)
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Apba2, amyloid beta (A4) precursor protein-binding, family A, member 2
Chromosome		7
Gene Common Name(s)		D15S1518E; HsT16821; LIN-10; MGC99508; MGC:14091; MINT2; Mint 2; X11-like; X11L;
Molecular Note		The exon encoding amino acids 368-416 of the phosphotyrosine binding (PTB) domain is flanked by loxP sites. A single FRT site, the remnant of an FRT-flanked neomycin resistance cassette (neo) previously removed by crossing mice with the cassette to mice expressing Flp recombinase in the germline, is present in the downstream intron. (Retention of the neo cassette ablates expression of this gene in mice.) Immunoblot analysis of brain homogenates demonstrates that mice with this conditional mutation express the protein at wild-type levels. [MGI Ref ID J:115573]
Allele Symbol		Apba3tm1Sud
Allele Name		targeted mutation 1, Thomas C Sudhof
Allele Type		Targeted (Floxed/Frt)
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Apba3, amyloid beta (A4) precursor protein-binding, family A, member 3
Chromosome		10
Gene Common Name(s)		AW208791; MGC:15815; Mint 3; Mint-3; Mint3; X11L2; X11gamma; expressed sequence AW208791; lin-10; neuron-specific X11L2 protein; neuronal munc18-1-interacting protein 3;
Molecular Note		Exon 3, encoding amino acids 201-249 of the phosphotyrosine binding (PTB) domain, is flanked by loxP sites. A single FRT site, the remnant of an FRT-flanked neomycin resistance cassette (neo) previously removed by crossing mice with the cassette to mice expressing Flp recombinase in the germline, is present in the downstream intron. (Retention of the neo cassette ablates expression of this gene in mice.) Immunoblot analysis of brain homogenates demonstrates that mice with this conditional mutation express the protein at wild-type levels. [MGI Ref ID J:115573]

Genotyping

Genotyping Information

Genotyping Protocols

Apba1^tm1Sud, Standard PCR
Apba2^tm1Sud, Standard PCR
Apba3^tm1Sud, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Ho A; Morishita W; Atasoy D; Liu X; Tabuchi K; Hammer RE; Malenka RC; Sudhof TC. 2006. Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family. J Neurosci 26(50):13089-101. [PubMed: 17167098]  [MGI Ref ID J:115573]

Additional References

Apba1^tm1Sud related

Ho A; Liu X; Sudhof TC. 2008. Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease. J Neurosci 28(53):14392-400. [PubMed: 19118172]  [MGI Ref ID J:142874]

Ho A; Morishita W; Hammer RE; Malenka RC; Sudhof TC. 2003. A role for Mints in transmitter release: Mint 1 knockout mice exhibit impaired GABAergic synaptic transmission. Proc Natl Acad Sci U S A 100(3):1409-14. [PubMed: 12547917]  [MGI Ref ID J:81845]

Apba2^tm1Sud related

Ho A; Liu X; Sudhof TC. 2008. Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease. J Neurosci 28(53):14392-400. [PubMed: 19118172]  [MGI Ref ID J:142874]

Apba3^tm1Sud related

Ho A; Liu X; Sudhof TC. 2008. Deletion of Mint proteins decreases amyloid production in transgenic mouse models of Alzheimer's disease. J Neurosci 28(53):14392-400. [PubMed: 19118172]  [MGI Ref ID J:142874]

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	When maintained as a live colony, triple homozygous floxed animals are intercrossed.

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. 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. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 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). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	None Available
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.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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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Terms of Use

Terms of Use

General Terms and Conditions

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Contact information

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