These mutant mice do not express the long or short isoforms of Beta 1,4-galactosyltransferase enzyme. 90% of homozygotes die soon after birth or within two to three weeks of birth. This mutant mouse strain may be useful in studies of glycosidic molecular interactions and function, and polyglandular endocrine insufficiency.
Barry D Shur, Emory University
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Ninety percent of homozygotes die soon after birth or within two to three weeks of birth. Surviving homozygotes are initially smaller than wild-type or heterozygotes and exhibit abnormal skin and coat, but assume a normal growth rate and appearance at three to four weeks of age. No gene product (mRNA) is detected by RT-PCR analysis of homozygous tissues. Neither the long or short isoform is expressed. Beta 1,4-galactosyltransferase enzyme activity is undetectable except for residual activity in brain and testis. Galactose residues are absent from testis. Heterozygotes have an intermediate enzyme activity level. Surviving homozygotes exhibit puffy faces (hypothyroid myxedema), thin skin, decreased density of hair follicles, reduction in subdermal adipose tissue, delayed spermatogenesis and incomplete lung development. Histological analysis reveals thick lung septa, small alveoli, diminished size and stratification of the adrenal cortex, and abnormally small anterior pituitary. Homozygous females are unable to deliver pups (dystocia) and do not lactate (agalactosis). Homozygous males are fertile. Sperm from homozygotes have increased binding to unfertilized eggs, bind ZP3 (zona pellucida glycoprotein 3) less and demonstrate poor zona pellucida penetration when compared to sperm from wild-type controls. Although able to undergo normal acrosomal exocytosis induced by calcium ionophore, homozygous sperm do not exhibit acrosome reaction to zona pellucida glycoproteins or anti-galactosyltransferase antibodies. Serum levels of thyroxine (T4) and T3 is reduced during the neonate period and then return to normal. Liver enzymes are elevated. This mutant mouse strain may be useful in studies of glycosidic molecular interactions and function, and polyglandular endocrine insufficiency.
This strain was transferred from the collection of the Consortium for Functional Glycomics.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 1.9kb of sequence from exon 1, which encodes all of the cytoplasmic and transmembrane domains as well as part of the extracellular region. The construct was electroporated into 129S7/SvEvBrd-Hprt1+ derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to C57BL/6J for 4 generations before arriving at The Jackson Laboratory. The mice were then crossed to C57BL/6J for one generation.
|Allele Name||targeted mutation 1, Barry D Shur|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||GalTase-null; gt -; total gt-|
|Gene Symbol and Name||B4galt1, UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1|
|Strain of Origin||129S7/SvEvBrd-Hprt+|
|Molecular Note||A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 1.9kb of sequence of exon 1, which encodes all of the cytoplasmic and transmembran domains as well as part of the extracellular region. Neither the long or short isoform of the encoded protein is expressed from this allele.|
|Mutations Made By|| |
Peter Sobieszczuk, Consortium for Functional Glycomics,TSRI
When maintaining a live colony, these mice can be bred as heterozygotes. Ninety percent of homozygotes die within 2-3 weeks of birth.
When using the B6.129S7-B4galt1tm1Shur/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #006941 in your Materials and Methods section.