129S6.129X1(B6)-Syt4^tm1Hahe/J

Stock number: 012400
Research areas: Neurobiology Research, Research Tools

Description

Mice that are homozygous for this targeted mutation may be useful in studies of learning, behavior and synaptic function and plasticity.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA) is detected by Northern blot analysis of total brain RNA. Homozygotes exhibit impaired locomotor coordination (reduced performance on accelerating rotarod), diminished contextual fear conditioning, impaired social transmission of food preference, enhanced long-term potentiation (LTP) and hyperactivity. Anxiety-like behavior and depression-like behavior is decreased in homozygous animals. Posterior pituitary nerve terminals isolated from homozygotes exhibit lower Ca2+ current density than wildtype controls, decreased exocytosis and accelerated endocytosis with high Ca2+ entry, and increased exocytosis with low Ca2+ entry. Hippocampal neurons isolated from homozygotes display increased rate of synpatic vesicle exocytosis from presynaptic terminals. Inner hair cells from homozygotes have abnormal exocytotic Ca2+ dependence. Mice that are homozygous for this targeted mutation may be useful in studies of learning, behavior and synaptic function and plasticity.

Development

A targeting vector containing a Neo cassette and herpes simplex virus thymidine kinase gene was used to disrupt an exon which encodes the first C2 domain. The construct was electroporated into 129X1/SvJ derived RW-4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to C57BL/6 female mice. The mice were backcrossed to C57BL/6 for several generations, then backcrossed to 129S6/SvEvTac for 7 or 8 generations (see SNP note below). Upon arrival at The Jackson Laboratory, mutant females and mutant males were bred together to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Markers on Chromosomes 8 and 13 are segregating, suggesting an incomplete backcross.

Allele

Symbol: Syt4^tm1Hahe
Name: targeted mutation 1, Harvey R Herschman
MGI accession ID: MGI:2180158
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Syt4
Marker name: synaptotagmin IV
Chromosome: 18
Strain of origin: 129X1/SvJ
Molecular note: The gene was disrupted by insertion of a neo resistance cassette into an exon encoding the first C2 domain. Northern blot of total brain RNA from homozygous mutant animals verified the absence of gene expression.