Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N4F9pN1   Donating Investigator Barry Shur,   Emory University

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.

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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of B4galt1

006941

B6.129S7-B4galt1tm1Shur/J

View Strains carrying other alleles of B4galt1     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

B4galt1^tm2Shur/B4galt1^tm2Shur

        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 B4Galt1^tm1Shur 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

View Research Applications

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

Genes & Alleles

Gene & Allele Information

Allele Symbol		B4galt1tm2Shur
Allele Name		targeted mutation 2, Barry D Shur
Allele Type		Targeted (knock-in)
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]

Genotyping

Genotyping Information

Genotyping Protocols

B4galt1^tm2Shur, Pyrosequencing

Helpful Links

Genotyping resources and troubleshooting

References

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

B4galt1^tm2Shur related

Steffgen K; Dufraux K; Hathaway H. 2002. Enhanced Branching Morphogenesis in Mammary Glands of Mice Lacking Cell Surface beta1,4-Galactosyltransferase. Dev Biol 244(1):114-33. [PubMed: 11900463]  [MGI Ref ID J:75957]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location). This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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Terms of Use

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