Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N5+ (23-JUL-08)   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
	Wild-type from the colony
	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)

Additional Web Information

Congenic Nomenclature

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, PYRO, vers. 1

Helpful Links

Optimizing PCR Protocols

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	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.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.