α-Gal A- mice contain a neo cassette replacing exon 3 and intron 3 of the galactosidase, alpha (Gla) gene, abolishing gene expression. These mice may be useful when studying the pathogenesis of Fabry disease.
Jeffrey Medin, Medical College of Wisconsin
α-Gal A- mice contain a neo cassette replacing exon 3 and intron 3 of the galactosidase, alpha (Gla) gene, abolishing gene expression. GLA is an X-linked gene that encodes a neuroendocrine peptide that is expressed in the central and peripheral nervous systems and also the gastrointestinal tract, pancreas, adrenal gland and urogenital tract. Mutations in GLA have been associated with the development of Fabry disease, a lysosomal storage disorder caused by a buildup of a fat called globotriaosylceramide (Gb3). Fabry disease is characterized by pain, particularly in the hands and feet (acroparesthesias), angiokeratomas, hypohidrosis, corneal opacity, gastrointestinal issues, tinnitus, and hearing loss. Fabry disease can also lead to life-threatening complications such as progressive kidney damage, heart attack, and stroke. Mutations have also been associated with Alzheimer's disease, epilepsy, depression, eating disorders, and impaired cognitive function.
Homozygous females and hemizygous males are viable and fertile.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype of these C57BL/6J-congenic mice could vary from that originally described on a B6;129 genetic background (Stock No. 003535). We may modify the strain description if necessary as published results become available. These mice are similar to the α-Gal A- mice in that they accumulate Gb3 in many organs, including liver, spleen, kidney and heart.
The α-Gal A- targeting vector was designed to replace exon 3 and intron 3 of the galactosidase, alpha (Gla) gene with a neomycin resistance (neo) cassette. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were maintained on a mixed genetic background prior to sending males to The Jackson Laboratory Repository to generate our colony of (Stock No. 003535) mice. Some of these mice were subsequently backcrossed to C57BL/6J mice (Stock No. 000664) for 6 generations in the laboratory of Dr. Jeff Medin (Medical College of Wisconsin). These mice were shipped back to The Jackson Laboratory as this new Stock No. 036174. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.
|Allele Name||targeted mutation 1, Ashok B Kulkarni|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||alpha-Gal A -/0; alpha-galA-; Gla-|
|Gene Symbol and Name||Gla, galactosidase, alpha|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A 1kb genomic fragment containing part of exon 3 and intron 3 was replaced by a neomycin resistance cassette.|
|Mutations Made By|| |
Ashok Kulkarni, NIDCR NIH
Gal is an X-linked gene. When maintaining a live colony, homozygous females may be bred to hemizygous males.
When using the B6 α-Gal A KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #036174 in your Materials and Methods section.