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Genes & Alleles

B4galt1;   B4galt1tm2Shur;

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Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic Additional information on JAX® GEMM® Strains. Type JAX® GEMM® Strain - Mutant Strain Type JAX® GEMM® Strain - Targeted Mutation Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Donating Investigator Barry Shur,   Emory University Generation N5+ (23-JUL-08)

Strain Description
These mice carry a mutant allele that has a point mutation in the first translation initiation codon in exon 1, which initiates translation of the long isoform of beta 1,4-galactosyltransferase. The second translation initiation codon in exon 1 is not affected. These mice express only the shorter isoform of beta 1,4-galactosyltransferase. No long isoform protein is detected in mammary tissue by Western blot analysis. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Total Beta 1,4-galactosyltransferase activity is reduced to 72% of wildtype levels in mammary gland epithelial cells while activity on mammary epithelial cell surfaces is diminished by over 60%. Sperm and testis exhibit near wildtype levels of enzyme activity and glycoprotein galactosylation. The short isoform is expressed ectopically in sperm. 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. Homozygous females exhibit abnormal mammary gland morphology including excessive mammary epithelial duct branching. Approximately 20% of homozygous females do not support their young. Mutants have elevated levels of expression of metalloproteinases (Mmp14 and Mmp7). Laminin espression in basal lamina is abnormal. This mutant mouse strain may be useful in studies of glycosidic molecular interactions and function, and cell-to-extracellular matrix (ECM) interactions.

This strain was transferred from the collection of the Consortium for Functional Glycomics.

Strain Development
A targeting vector containing a neomycin resistance and herpes simplex virus thymidine kinase genes was used to insert a point mutation into the first translation initiation codon in exon 1, which initiates translation of the long isoform. 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.

Mammalian Phenotype Terms assigned by genotype The following phenotype information may relate to a genetic background differing from this JAX® Mice strain. B4galt1tm2Shur/B4galt1tm2Shur         involves: 129S7/SvEvBrd * C57BL/6J reproductive system phenotype abnormal branching of the mammary ductal tree (MGI Ref ID J:75957) mammary glands exhibit increased branching and increased density of ducts; interbranch distance is significantly reduced by >40% compared to wild type abnormal fertilization (MGI Ref ID J:43773) males are fertile, but their sperm binds to the zona with much greater efficacy than wild-type sperm impaired acrosome reaction (MGI Ref ID J:43773) sperm do not respond to B1,4-galacosyltransferase or zona pellucida proteins in an acrosome reaction, but response to calcium ionophore is normal abnormal mammary gland growth during pregnancy (MGI Ref ID J:75957) at day 15 of pregnancy, glands show increased density of alveoli compared to wild-type, as well as an abnormal branching pattern incidence of alveolar budding and side branches along the ducts is significantly increased, resulting in multiple alveoli along epithelial ducts in between side branches glands display precocious differentiation; alveolar epithelia have increased numbers of secretory vesicles at day 15 of pregnancy compared to wild-type mice abnormal milk composition (MGI Ref ID J:75957) alpha-lactalbumin is elevated 2-fold in mutant mammary glands at day 17 of pregnancy; beta-casein and whey acidic protein are elevated, but not statistically significantly compared to wild-type endocrine/exocrine gland phenotype abnormal branching of the mammary ductal tree (MGI Ref ID J:75957) mammary glands exhibit increased branching and increased density of ducts; interbranch distance is significantly reduced by >40% compared to wild type abnormal mammary gland growth during pregnancy (MGI Ref ID J:75957) at day 15 of pregnancy, glands show increased density of alveoli compared to wild-type, as well as an abnormal branching pattern incidence of alveolar budding and side branches along the ducts is significantly increased, resulting in multiple alveoli along epithelial ducts in between side branches glands display precocious differentiation; alveolar epithelia have increased numbers of secretory vesicles at day 15 of pregnancy compared to wild-type mice abnormal milk composition (MGI Ref ID J:75957) alpha-lactalbumin is elevated 2-fold in mutant mammary glands at day 17 of pregnancy; beta-casein and whey acidic protein are elevated, but not statistically significantly compared to wild-type homeostasis/metabolism phenotype *normal* homeostasis/metabolism phenotype (MGI Ref ID J:43773) mice do not display endocrine insufficiency like B4Galt1tm1Shur mice; anterior pituitary hormones have normal glycosylation abnormal enzyme/coenzyme activity (MGI Ref ID J:75957) in cultured mammary epithelial cells, total enzyme activity (B1,4-galacosyltransferase ) is reduced by ~28% compared to wild-type cells; activity on surface of mammary epithelial cells is reduced ~60% relative to wild-type cells

Gene & Allele Details

Allele Symbol		B4galt1tm2Shur
Allele Name		targeted mutation 2, Barry D Shur
Common Name(s)		GalT-null; Long GalT-Null; long gt<-/->;
Mutation Made By		Peter Sobieszczuk,   Consortium for Functional Glycomics,TSRI
Strain of Origin		129S7/SvEvBrd-Hprt1<+>
ES Cell Line Name		AB1
ES Cell Line Strain		129S7/SvEvBrd-Hprt1<+>
Gene Symbol and Name		B4galt1, UDP-Gal:betaGlcNAc beta 1,4- galactosyltransferase, polypeptide 1
Chromosome		4
Gene Common Name(s)		AA407245; B-1,4-GalT1; B4GAL-T1; DKFZp686N19253; GGTB2; GT1; GTB; GalT; Ggtb; Ggtb2; MGC50983; b1,4-Galactosyltransferase I; beta 1,4-Galactosyltransferase I; beta-1,4-GalT1; beta4Gal-T1; expressed sequence AA407245; galactosyltransferase 2 beta 1, 4; glycoprotein galactosyltransferase beta 1, 4;
Molecular Note		A targeting vector containing a neomycin resistance and herpes simplex virus thymidine kinase genes was used to insert a point mutation into the first translation initiation codon in exon 1, which initiates translation of the long isoform. Expressionof the long isoform is eliminated. Expression of the short isoform is unaffected. [MGI Ref ID J:43773]

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Diet Information	LabDiet® 5K52/5K67

Related Strains

Strains carrying other alleles of B4galt1

006941

B6.129S7-B4galt1tm1Shur/J

View Strains carrying other alleles of B4galt1     (1 strain)

Additional Web Information

Congenic Nomenclature

Research Applications

This mouse can be used to support research in many areas including:

Cell Biology Research
Defects in Extracellular Matrix Molecules
Protein Processing

Endocrine Deficiency Research
Gonad Defects
Mammary Gland Defects

Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads

References

Selected Reference(s)

Lu Q; Shur BD. 1997. Sperm from beta 1,4-galactosyltransferase-null mice are refractory to ZP3-induced acrosome reactions and penetrate the zona pellucida poorly. Development 124(20):4121-31. [PubMed: 9374408]  [MGI Ref ID J:43773]

Additional References

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Price and Supply Information

Strain Name:	B6.129S7-B4galt1tm2Shur/J
Stock Number:	006943

 

This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.

Estimated Available for Sale Date:

Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.

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Supply Details

Standard Supply	Under Development for Distribution Colony
Supply Notes	This strain is included in the Induced Mutant Resource Colony collection.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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