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 N6pN1 Generation Definitions   Donating Investigator Kevin Campbell,   University of Iowa

Description
Heterozygotes are viable and fertile, but homozygous embryos exhibit gross developmental abnormalities beginning around 6.5 days of gestation. This lethality is attributed to a disruption of Reichert’s membrane, an extra-embryonic basement membrane. Laminin and collagen IV are specifically disrupted. No detectable transcript or protein is produced from this allele in homozygous embryos. Northern blot analysis of skeletal muscle RNA shows that transcript levels in heterozygotes are only 10-20% lower than those in wild-type mice. This mutant mouse strain represents a model that may be useful in studies of muscular dystrophies linked to dystrophin-glycoprotein complexes, and developmental processes.

Development
A targeting vector containing a neomycin resistance gene was use to replace a 5' portion of exon 2, including the splice acceptor site and a large part of the coding sequence. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric animals were crossed with C57BL/6. The strain was been backcrossed to C57BL/6 six times by the donating laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Dag1

006835	129-Dag1tm2Kcam/J
009652	B6.129(Cg)-Dag1tm2.1Kcam/J
006834	B6.129-Dag1tm2Kcam/J

View Strains carrying other alleles of Dag1     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Muscular Dystrophy-Dystroglycanopathy (limb-Girdle), Type C, 9; MDDGC9   (DAG1)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

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

Dag1^tm1Kcam/Dag1^tm1Kcam

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J   (conditional)

• mortality/aging
• partial embryonic lethality during organogenesis
  • most homozygotes are substantially resorbed by E10.5   (MGI Ref ID J:40601)
• embryogenesis phenotype
• abnormal embryonic tissue morphology
  • starting at E6.5, homozygotes typically have a significantly smaller embryonic region   (MGI Ref ID J:40601)
  • only a small mass of embryonic tissue is detected at E10.5   (MGI Ref ID J:40601)
• • absent mesoderm
    • at E7.5, homozygotes lack any identifiable mesodermal tissue   (MGI Ref ID J:40601)
• abnormal extraembryonic tissue morphology   (MGI Ref ID J:40601)
• • abnormal Reichert's membrane morphology
    • at E6.5, homozygotes lack a continuous Reichert's membrane; maternal red blood cells are thus found in the yolk sac cavity as early as E5.5   (MGI Ref ID J:40601)
    • only occasional "patches" of laminin and collagen IV, two major structural elements of Reichert's membrane, are detected   (MGI Ref ID J:40601)
    • in contrast, the basement membrane between the visceral endoderm and ectoderm appears normal   (MGI Ref ID J:40601)
    • Reichert's membrane defects are not due to a lack of parietal endoderm   (MGI Ref ID J:40601)
  • absent extraembryonic ectoderm
    • at E6.5, homozygotes lack any significant development of extraembryonic ectoderm   (MGI Ref ID J:40601)
    • in contrast, visceral endoderm and a well-formed pro-amniotic cavity are clearly evident   (MGI Ref ID J:40601)
• decreased embryo size
  • by E7.5, homozygous mutant embryos are much smaller than wild-type embryos   (MGI Ref ID J:40601)
• embryonic growth arrest
  • homozygotes fail to progress beyond the early egg cylinder stage of development   (MGI Ref ID J:40601)
  • however, early differentiation of extraembryonic lineages and implantation appear unaffected   (MGI Ref ID J:40601)
• failure to gastrulate
  • homozygotes fail to gastrulate   (MGI Ref ID J:40601)
• growth/size phenotype
• decreased embryo size
  • by E7.5, homozygous mutant embryos are much smaller than wild-type embryos   (MGI Ref ID J:40601)

View Research Applications

Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)

Neurobiology Research
Muscular Dystrophy

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Dag1tm1Kcam
Allele Name		targeted mutation 1, Kevin P Campbell
Allele Type		Targeted (knock-out)
Common Name(s)		DG-; Dag1neo2;
Mutation Made By		Kevin Campbell,   University of Iowa
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Dag1, dystroglycan 1
Chromosome		9
Gene Common Name(s)		156DAG; A3a; AGRNR; D9Wsu13e; DAG; DG; DNA segment, Chr 9, Wayne State University 13, expressed; MDDGC7; MDDGC9; alpha-dystroglycan; beta-dystroglycan; dystrophin associated glycoprotein 1;
Molecular Note		A neomycin resistance gene replaced part of exon 2, including the splice acceptor site and a large part of the coding sequence. No detectable transcript was produced from this allele in homozygous embryos (data not shown) and immunohistochemistry experiments on homozygous embryos confirmed that no detectable encoded protein was present. [MGI Ref ID J:40601]

Genotyping

Genotyping Information

Genotyping Protocols

Dag1^tm1Kcam, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Williamson RA; Henry MD; Daniels KJ; Hrstka RF; Lee JC; Sunada Y ; Ibraghimov-Beskrovnaya O ; Campbell KP. 1997. Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice. Hum Mol Genet 6(6):831-41. [PubMed: 9175728]  [MGI Ref ID J:40601]

Additional References

Dag1^tm1Kcam related

Cohn RD; Henry MD; Michele DE; Barresi R; Saito F; Moore SA; Flanagan JD; Skwarchuk MW; Robbins ME; Mendell JR; Williamson RA; Campbell KP. 2002. Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration. Cell 110(5):639-48. [PubMed: 12230980]  [MGI Ref ID J:78838]

Moore SA; Saito F; Chen J; Michele DE; Henry MD; Messing A; Cohn RD; Ross-Barta SE; Westra S; Williamson RA; Hoshi T; Campbell KP. 2002. Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418(6896):422-5. [PubMed: 12140559]  [MGI Ref ID J:86901]

Wright KM; Lyon KA; Leung H; Leahy DJ; Ma L; Ginty DD. 2012. Dystroglycan organizes axon guidance cue localization and axonal pathfinding. Neuron 76(5):931-44. [PubMed: 23217742]  [MGI Ref ID J:194150]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, heterozygotes are crossed.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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