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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Former Names B6;129S7-Akp2tm1Sor/J (Changed: 27-DEC-07 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Grant MacGregor, University of California, Irvine Description
Mice heterozygous for the Alpltm1Sor targeted mutation appear normal and viable. Homozygous mutant mice are perinatal lethals but can be rescued by pyridoxal treatment. Surviving homozygotes develop epilepsy due to reduced GABA levels in the brain. Bone formation does not appear to be grossly affected in untreated animals, but treated animals exhibit cranial dysmorphology. The targeting vector contained both a b-galalactosidase and a neomycin genes (beta-geo), both of which are under the control of the Alpl promoter and are thus expressed in a tissue specific manner. Specifically, expression occurs in developing bones and in primordial germ cells (PGC), and the beta-galactosidase thus serves as a marker for these tissues. The marker for PGC's is particularly significant because the current marker (alkaline phosphatase staining) is only useful to study early germ cell migration.Development
This targeted mutant was made in the laboratory of Dr. Phillipe Soriano by Dr. Grant MacGregor (currently at Emory University School of Medicine). A lacZ/neo (beta-geo) targeting vector was used which substituted a portion of the Alpl gene.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (178 strains)
002484 129-Alpltm1Sor/J 002741 B6.129S7-Alpltm1Sor/J
008569 129-Alpltm1(cre)Nagy/J
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
Hypophosphatasia, Adult - Models with phenotypic similarity to human disease where etiologies involve orthologs.1 Hypophosphatasia, Childhood - Models with phenotypic similarity to human disease where etiologies involve orthologs.1 Hypophosphatasia, Infantile - Models with phenotypic similarity to human disease where etiologies involve orthologs.1
1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
assigned by genotype
Alpltm1Sor/Alpltm1Sor
either: (involves: 129S7/SvEvBrd-Alpltm1Sor) or (involves: 129S7/SvEvBrd * C57BL/6)
- lethality-postnatal
- postnatal lethality (MGI Ref ID J:28394)
- attributed to development of seizures at 2 weeks of age
- behavior/neurological phenotype
- seizures (MGI Ref ID J:28394)
- develop at 2 weeks of age
- craniofacial phenotype
- abnormal tooth morphology (MGI Ref ID J:28394)
- in mice rescued by pyridoxal supplementation to repair PLP defect, exhibit defective tooth and enamel formation
- growth/size phenotype
- decreased body size (MGI Ref ID J:28394)
- size ranged from 50 - 100% of heterozygous or wild-type littermates
- homeostasis/metabolism phenotype
- abnormal blood chemistry (MGI Ref ID J:28394)
- elevated serum concentration of pyridoxal 5' phosphate (PLP), results in decreased GABA concentrations in the brain
- elevated serum concentration of phosphoethanolamine (PEA)
- nervous system phenotype
- seizures (MGI Ref ID J:28394)
- develop at 2 weeks of age
This mouse can be used to support research in many areas including:
Alpltm1Sor relatedDevelopmental Biology Research
Perinatal Lethality (Homozygous)
Skeletal Defects (human infantile hypophosphatasia model)
Neurobiology Research
Epilepsy
Research Tools
lacZ Expression
Developmental Biology Research
Neurobiology Research (cell marker)
Cancer Research
Genes Regulating Growth and Proliferation
Metabolism Research
Vitamin B-6 Metabolism Defects
Neurobiology Research
Epilepsy
Metabolic Defects (vitamin B-6 metabolism defects)
Research Tools
Genetics Research (Tissue/Cell Markers: primordial germ cell marker)
Reproductive Biology Research (primordial germ cell marker)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Alpltm1Sor | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Philippe Soriano | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | TNAP-bgeo; Tnap-; | ||
| Mutation Made By | Grant MacGregor, University of California, Irvine | ||
| Strain of Origin | 129S7/SvEvBrd-Hprt1<+> | ||
| ES Cell Line Name | AB1 | ||
| ES Cell Line Strain | 129S7/SvEvBrd-Hprt1<+> | ||
| Site of Expression | lacZ expression is detected in developing bones and in primordial germ cells (PGC). | ||
| Gene Symbol and Name | Alpl, alkaline phosphatase, liver/bone/kidney | ||
| Chromosome | 4 | ||
| Gene Common Name(s) | AP-TNAP; Akp-2; Akp2; FLJ40094; FLJ93059; HOPS; MGC161443; MGC167935; MGC93545; PHOA; TNAP; TNSALP; alkaline phosphatase 2, liver; | ||
| General Note | Akp2tm1Sor, alkaline phosphatase 2, targeted mutaton 1, Philippe Soriano. Only the embryonic (EAP) and tissue non-specific (TNAP) forms of alkaline phosphatase are expressed in mouse embryos. EAP is the predominant form of the enzyme in the early embryo, but predominance switches to TNAP about the 7th embryonic day. Akp2tm1Sor was used to clarify the expression of TNAP in mouse primordial germ cells. These cells do not express TNAP before gastrulation, but the enzyme is elaborated by extraembryonic tissue prior to that stage. Primordial germ cells do not require TNAP for either development or migration (J:25249).Although a lack of TNAP causes defects in human skeletal mineralization, Akp2tm1Sor homozygous mice develop skeletons normal at birth. But at approximately 2 weeks after birth, these mice develop seizures leading to a fatal outcome. The seizures arise from faulty metabolism of pyridoxal (vitamin B6), and can be rescued by administration of pyridoxal. Rescued survivors later develop defects in dentition (J:28394). | ||
| Molecular Note | A neomycin cassette replaced 1.6 kb of the gene, from a portion of exon 2 to a portion of exon 6. The construct deleted the active site of the protein, Ser 93, located in exon 5. RT-PCR of total RNA from E13 gonads of homozygous mutant mice did not detect transcript. In addition, lack of protein in homozygous mutant mice was demonstrated functionally. [MGI Ref ID J:25249] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Alpltm1Sor, STD PCR, vers. 3
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
MacGregor GR; Zambrowicz BP; Soriano P. 1995. Tissue non-specific alkaline phosphatase is expressed in both embryonic and extraembryonic lineages during mouse embryogenesis but is not required for migration of primordial germ cells. Development 121(5):1487-96. [PubMed: 7789278] [MGI Ref ID J:25249]
Additional References
Fedde KN; Blair L; Silverstein J; Coburn SP; Ryan LM; Weinstein RS; Waymire K; Narisawa S; Millan JL; MacGregor GR; Whyte MP. 1999. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 14(12):2015-26. [PubMed: 10620060] [MGI Ref ID J:78130]
Hessle L; Johnson KA; Anderson HC; Narisawa S; Sali A; Goding JW; Terkeltaub R; Millan JL. 2002. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A 99(14):9445-9. [PubMed: 12082181] [MGI Ref ID J:77731]
Waymire KG; Mahuren JD; Jaje JM; Guilarte TR; Coburn SP; MacGregor GR. 1995. Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat Genet 11(1):45-51. [PubMed: 7550313] [MGI Ref ID J:28394]
Alpltm1Sor relatedBeertsen W; VandenBos T; Everts V. 1999. Root development in mice lacking functional tissue non-specific alkaline phosphatase gene: inhibition of acellular cementum formation. J Dent Res 78(6):1221-9. [PubMed: 10371245] [MGI Ref ID J:55788]
Fedde KN; Blair L; Silverstein J; Coburn SP; Ryan LM; Weinstein RS; Waymire K; Narisawa S; Millan JL; MacGregor GR; Whyte MP. 1999. Alkaline phosphatase knock-out mice recapitulate the metabolic and skeletal defects of infantile hypophosphatasia. J Bone Miner Res 14(12):2015-26. [PubMed: 10620060] [MGI Ref ID J:78130]
Murshed M; Harmey D; Millan JL; McKee MD; Karsenty G. 2005. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev 19(9):1093-104. [PubMed: 15833911] [MGI Ref ID J:98452]
Tesch W; Vandenbos T; Roschgr P; Fratzl-Zelman N; Klaushofer K; Beertsen W; Fratzl P. 2003. Orientation of mineral crystallites and mineral density during skeletal development in mice deficient in tissue nonspecific alkaline phosphatase. J Bone Miner Res 18(1):117-25. [PubMed: 12510812] [MGI Ref ID J:111194]
Waymire KG; Mahuren JD; Jaje JM; Guilarte TR; Coburn SP; MacGregor GR. 1995. Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6. Nat Genet 11(1):45-51. [PubMed: 7550313] [MGI Ref ID J:28394]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry Mice are maintained by mating heterozgyous siblings or heterozygous carriers to wildtype littermate controls. Homozygous mutant mice may be recovered by injection of pyridoxal. Success using this treatment very dependent on dosage. Information from the originating investigator also suggests that the type of diet and preparation may be important for maintenance of the strain. He suggests Purina autoclavable 5021. Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
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*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
Additional Supply Details
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 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
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