The dyW (dyw) knock-in/knockout allele was designed to both abolish laminin alpha 2 (Lama2; merosin) expression and direct lacZ expression by the endogenous Lama2 promoter/enhancer elements. Merosin is normally expressed in striated muscle, peripheral and central nervous systems, thymus, thyroid, intestine, and testis. These dyW mice may be useful for studying merosin-deficient congenital muscular dystrophy and other muscular dystrophies.
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Eva Engvall, Sanford-Burnham Medical Research Institu
Genetic Background | Generation |
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N8+pN1
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Lama2 | laminin, alpha 2 |
A targeting vector was designed to insert a β-galactosidase (lacZ) gene and a neomycin (neo) resistance cassette downstream of the start codon of the laminin, alpha 2 (Lama2) gene, abolishing gene function. Heterozygous dyW mice are viable, fertile and normal in size, Homozygous mice exhibit growth retardation and most die between 2-4 weeks of age. Laminin2 (merosin) is normally expressed in striated muscle, peripheral and central nervous systems, thymus, thyroid, intestine, and testis and has been associated with merosin-deficient congenital muscular dystrophy (MCMD). Homozygous dyW mice are passive, small, and emaciated, and demonstrate partial hindleg lameness and clasping. Their muscles contain necrotic fibers with occasional areas of regeneration, and they exhibit pronounced fibrosis and increased creatine kinase (CK) activity. When heterozygous dyW mice are bred with transgenic mice expressing the mouse muscle creatine kinase (Ckm or Mck) promoter driving the expression of human LAMA2 gene, the MCMD phenotype was rescued. These transgenic dyW mice still become increasingly paralyzed with age and develop hindlimb contractures similar to nontransgenic dyW mice. These dyW mutant mice may be useful for studying merosin deficiency in MCMD and other muscular dystrophies.
A targeting vector was designed to insert a β-galactosidase (lacZ) and neomycin (neo) resistance cassette downstream of the start codon of the laminin, alpha 2 (Lama2) gene. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric males were bred to Black Swiss females to generate the mutant colony. These mutant mice were then backcrossed to C57BL/6 for at least four generations to produce a colony of dyW mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony. A high-density SNP (single nucleotide polymorphism) panel analysis was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed the mice were ~90% C57BL/6 allele-type. After this, mice were additionally backcrossed to C57BL/6J inbred mice using a marker-assisted speed congenic approach to complete this congenic line.
Expressed Gene | lacZ, beta-galactosidase, E. coli |
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Site of Expression |
Allele Name | targeted mutation 1, Eva Engvall |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | dyw; Lama2-; Lama2dy-W |
Gene Symbol and Name | Lama2, laminin, alpha 2 |
Gene Synonym(s) | |
Expressed Gene | lacZ, beta-galactosidase, E. coli |
Strain of Origin | 129S1/Sv-Oca2+ Tyr+ Kitl+ |
Chromosome | 10 |
Molecular Note | Insertion of a lacZ and neomycin resistance cassette 23 bp downstream of the ATG start site disrupts gene transcription. |
Mutations Made By | Eva Engvall, Sanford-Burnham Medical Research Institu |
Mutant mice were bred to C57BL/6J inbred mice (Stock No. 000664) for many generations using a marker-assisted speed congenic approach to establish this congenic strain. When maintaining the live congenic colony, heterozygous mice may be bred to wildtype mice from the colony, or to C57BL/6J inbred mice. Homozygotes exhibit growth retardation, hindlimb paralysis, and most die by 2-4 weeks of age.
When using the dyW mouse strain in a publication, please cite the originating article(s) and include JAX stock #013786 in your Materials and Methods section.
Facility Barrier Level Descriptions
AX18 (Maximum) |
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Lama2<tm1Eeng> |
Frozen Mouse Embryo | B6.129S1(Cg)-Lama2<tm1Eeng>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S1(Cg)-Lama2<tm1Eeng>/J | $2595.00 |
Frozen Mouse Embryo | B6.129S1(Cg)-Lama2<tm1Eeng>/J | $3373.50 |
Frozen Mouse Embryo | B6.129S1(Cg)-Lama2<tm1Eeng>/J | $3373.50 |
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