These Mint triple-floxed mice may be useful for generating conditional mutations in applications relating to neurotransmission.
Dr. Thomas C. Sudhof, Stanford University School of Medicine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), No functional change) | Apba1 | amyloid beta (A4) precursor protein binding, family A, member 1 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), No functional change) | Apba2 | amyloid beta (A4) precursor protein-binding, family A, member 2 |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), No functional change) | Apba3 | amyloid beta (A4) precursor protein-binding, family A, member 3 |
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.
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.
Allele Name | targeted mutation 1, Thomas C Sudhof |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | |
Gene Symbol and Name | Apba1, amyloid beta (A4) precursor protein binding, family A, member 1 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 19 |
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. |
Mutations Made By | Dr. Thomas Sudhof, Stanford University School of Medicine |
Allele Name | targeted mutation 1, Thomas C Sudhof |
---|---|
Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | |
Gene Symbol and Name | Apba2, amyloid beta (A4) precursor protein-binding, family A, member 2 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 7 |
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. |
Allele Name | targeted mutation 1, Thomas C Sudhof |
---|---|
Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | |
Gene Symbol and Name | Apba3, amyloid beta (A4) precursor protein-binding, family A, member 3 |
Gene Synonym(s) | |
Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl+ |
Chromosome | 10 |
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. |
When maintained as a live colony, triple homozygous floxed animals are intercrossed.
When using the Mint triple-floxed mouse strain in a publication, please cite the originating article(s) and include JAX stock #006394 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Homozygous for Apba2<tm1Sud>, Homozygous for Apba3<tm1Sud>,Homozygous for Apba1<tm1Sud> |
Frozen Mouse Embryo | B6;129-Apba2<tm1Sud> Apba3<tm1Sud> Apba1<tm1S Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;129-Apba2<tm1Sud> Apba3<tm1Sud> Apba1<tm1S Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;129-Apba2<tm1Sud> Apba3<tm1Sud> Apba1<tm1S Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6;129-Apba2<tm1Sud> Apba3<tm1Sud> Apba1<tm1S Frozen Embryos | $3373.50 |
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