STOCK Smtnl1^tm1Tajh/J

Stock number: 010503
Research areas: Cardiovascular Research, Metabolism Research

Description

This targeted mutation of the smoothelin-like 1 (Smtnl1) gene displays an abnormal response to exercise adaptation in muscle fibers and may be useful in studies of muscle and vascular adaptation to exercise.

Detailed description

Mice homozygous for this targeted mutation are viable, fertile and normal in size. No gene product is detected by Western blot analysis. Mutant mice exhibit better performance during endurance training and, males in particular, exhibit increased time to fatigue, distance run and vertical work in stress tests after endurance training. Vasorelaxation and contractile responses are improved in mutant mice and the ratio of type 2a muscle fibers is increased in sedentary mice, however, this ratio does not change following exercise. This mutant mouse strain may be useful in studies of muscle and vascular adaptation to exercise.

Development

A targeting vector was designed to replace exons 3-8 of the targeted gene with a neomycin resistance cassette. The construct was electroporated into 129P2/OlaHsd-derived E14TG2A embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient C57BL/6 blastocysts, and chimeric males were bred to 129S6/SvEvTac females. Heterozygous offspring were bred to 129S6/SvEvTac mice for approximately 11 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation prior to intercrossing to generate homozygotes.

A 27 SNP (single nucleotide polymorphism) panel analysis performed by The Jackson Laboratory revealed 3 of 27 markers (on chromsomes 1, 13 and 15) that were not 129 allele-type. These data suggest genetic contamination (perhaps from C57BL/6 or other) prior to arrival at The Jackson Laboratory.

Allele

Symbol: Smtnl1^tm1Tajh
Name: targeted mutation 1, Timothy A J Haystead
MGI accession ID: MGI:3796616
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Smtnl1
Marker name: smoothelin-like 1
Chromosome: 2
Strain of origin: 129P2/OlaHsd
Molecular note: Exons 3 through 8, which encode amino acids 230-421, were replaced with a neo cassette. The absence of protein product was confirmed by western blot on skeletal muscle extracts.