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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+5p Generation Definitions   Donating Investigator Dr. Thomas C. Sudhof,   Stanford University School of Medicine

Description
These compound mutant mice carry targeted mutations of the Stx1a (syntaxin 1A (brain)) and Stx1b (syntaxin 1B) genes. Stx1a mutant (XRA) homozygous mice do not show any abnormality of their own, but in combination with the Stx1b hypomorph mutation (XTB) (see Stock No. 008138), XRA worsens the XRB phenotype. Double homozygous mice die prenatally, show a 40% reduction in syntaxin binding protein (Munc-18) levels and have small Purkinje cells in cerebellum.

Development
This compound mutant strain was created by crossing "XRA" (Stx1a mutant) mice with "XRB" (Stx1b mutant) mice.

To create the XRA mice (see Stock No. 008137), a targeting vector was used to introduce a Flp-flanked neomycin resistance cassette to intron 1 and a loxP-flanked green fluorescent protein (GFP) segment to exon 2 of the gene. The GFP segment was deleted from targeted animals through crosses with a Cre strain. The background of this mouse has not been indicated. Upon arrival, mice were bred to C57BL/6J mice for at least one generation to establish the colony.

The XRB mice were derived from XTB mice (see Stock No. 008138). XTB mice were created using a vector designed to introduce two modified copies of exon 7 to the targeted gene. The first modified exon 7 carries a partial cDNA fragment of syntaxin with a C-terminal GFP and a stop codon. This mutation is followed by neomycin resistance cassette placed in intron 7 and flanked by flp sites. The first exon 7 insertion and the neomycin cassette are flanked by a pair of Frt sites. A second modified exon 7 bearing L165A and E166A mutations follows the neomycin insertion. The background of this mouse has not been indicated. Upon arrival, mice were bred to C57BL/6J mice for at least one generation to establish the colony. To create the XRB line, crosses with a mixed C57BL/6 and 129 background Cre strain excised the floxed region (incorporating the exon 7 GFP knock-in and neomycin cassette).

The two independent XRA and XRB lines were intercrossed to create this compound mutant line.

Related Strains

Strains carrying   Stx1a^tm1.1Sud allele

008137

STOCK Stx1atm1.1Sud/J

View Strains carrying   Stx1a^tm1.1Sud     (1 strain)

Strains carrying other alleles of Stx1a

007880	B6SJL-Tg(Thy1-Stx1a/EYFP)1Sud/J
007879	STOCK Stx1atm2Sud/J

View Strains carrying other alleles of Stx1a     (2 strains)

Strains carrying other alleles of Stx1b

008138

STOCK Stx1btm1Sud/J

View Strains carrying other alleles of Stx1b     (1 strain)

Phenotype

Phenotype Information

View Research Applications

Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)
Neurodevelopmental Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Stx1atm1.1Sud
Allele Name		targeted mutation 1.1, Thomas C Sudhof
Allele Type		Targeted (knock-out)
Common Name(s)		XRA;
Mutation Made By		Dr. Thomas Sudhof,   Stanford University School of Medicine
Gene Symbol and Name		Stx1a, syntaxin 1A (brain)
Chromosome		5
Gene Common Name(s)		HPC-1; P35-1; STX1; SYN1A;
Molecular Note		A targeting vector was used to introduce a Flp-flanked neomycin resistance cassette to intron 1 and a loxP-flanked green fluorescent protein (GFP) segment to exon 2 of the gene. The GFP segment was deleted from targeted animals through crosses with a Crestrain. [MGI Ref ID J:144771]
Allele Symbol		Stx1btm1.1Sud
Allele Name		targeted mutation 1.1, Thomas C Sudhof
Allele Type		Targeted (Reporter)
Common Name(s)		XRB; syntaxin-1BOpen;
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Stx1b, syntaxin 1B
Chromosome		7
Gene Common Name(s)		STX1B1; STX1B2; Stx1b2; Stx2; syntaxin 1B2;
Molecular Note		Mice carrying the XTB allele were crossed to protamine-cre expressing animals and germ line cre-meditated excised the endogenous exon 7 carrying the GFP insert with the neomycin-selection cassette, leaving the mutated one behind. The resulting allele encodes the 'open' syntaxin-1B protein conformation. [MGI Ref ID J:138035]

Genotyping

Genotyping Information

Genotyping Protocols

Stx1b^tm1.1Sud < STD PCR < 1 < VALIDATED, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gerber SH; Rah JC; Min SW; Liu X; de Wit H; Dulubova I; Meyer AC; Rizo J; Arancillo M; Hammer RE; Verhage M; Rosenmund C; Sudhof TC. 2008. Conformational Switch of Syntaxin-1 Controls Synaptic Vesicle Fusion. Science 321(5895):1507-10. [PubMed: 18703708]  [MGI Ref ID J:138035]

Additional References

Stx1a^tm1.1Sud related

Sudhof TC. 2009. Generation of an Stx1a mutant allele MGI Direct Data Submission :.  [MGI Ref ID J:144771]

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 maintained as a live colony animals homozygous for the Stx1a mutation and heterozygous for the Stx1b2 mutation may be intercrossed. Animals homozygous for the Stx1b2 mutation die around postnatal day 30 due to seizures.

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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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