These Alpl knock-out mice exhibit perinatal lethality with survivors developing epilepsy.
Dr. Grant MacGregor, University of California, Irvine
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Alpl | alkaline phosphatase, liver/bone/kidney |
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.
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.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression | lacZ expression is detected in developing bones and in primordial germ cells (PGC). |
Allele Name | targeted mutation 1, Philippe Soriano |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Tnap-; TN-APBetageo; TNAP-bgeo |
Gene Symbol and Name | Alpl, alkaline phosphatase, liver/bone/kidney |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Site of Expression | lacZ expression is detected in developing bones and in primordial germ cells (PGC). |
Strain of Origin | 129S7/SvEvBrd-Hprt+ |
Chromosome | 4 |
General Note | 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). |
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. |
Mutations Made By | Dr. Grant MacGregor, University of California, Irvine |
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.
When using the TNAPβgeo mouse strain in a publication, please cite the originating article(s) and include JAX stock #002484 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
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Heterozygous or Wild-type for Alpl<tm1Sor> |
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