129-Alpl^tm1Sor/J

Stock number: 002484
Product name: TNAP^βgeo
Research areas: Cancer Research, Developmental Biology Research, Metabolism Research, Neurobiology Research, Research Tools

Description

These Alpl knock-out mice exhibit perinatal lethality with survivors developing epilepsy.

Detailed description

Mice heterozygous for the Alpl^tm1Sor 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.

Allele

Symbol: Alpl^tm1Sor
Name: targeted mutation 1, Philippe Soriano
MGI accession ID: MGI:1857124
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Alpl
Marker name: alkaline phosphatase, liver/bone/kidney
Chromosome: 4
Strain of origin: 129S7/SvEvBrd-Hprt⁺
Expressed genes: lacZ,beta-galactosidase,E. coli
Site of expression: lacZ expression is detected in developing bones and in primordial germ cells (PGC).
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.
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. Akp2^tm1Sor 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).