B6.Cg-Uba6^tm1Whpr/J

Stock number: 021506
Research areas: Cell Biology Research, Neurobiology Research, Research Tools

Description

These Uba6^flox/flox mutant mice possess loxP sites flanking exons 16-17 of the targeted gene. This strain may be useful for studying the regulation of protein homeostasis during development.

Detailed description

These Uba6^flox/flox mutant mice possess loxP sites flanking exons 16-17 of the ubiquitin-like modifier activating enzyme 6 (Uba6) gene. Uba6 (E1) is part of the ubiquitin proteasome system (UPS) which regulates protein homeostasis during development. Complete UBA6 deficiency leads to embryonic arrest by E5.5. Mice that are homozygous for this floxed-allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-6 deleted in the cre-expressing tissues.

For example, when bred to B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771), resulting mice lack neuronal UBA6 and display altered neuronal patterning in the hippocampus and the amygdala, decreased dendritic spine density, and numerous behavioral disorders. They also contain altered levels of ubiquitin protein ligase E3A (Ube3a) and SH3/ankyrin domain gene 3 (Shank3) spine proteins.

Development

A targeting vector was designed to insert a loxP site upstream of exon 16, and a second loxP site, followed by a frt-flanked neomycin resistance (neo) cassette, downstream of exon 17 of the ubiquitin-like modifier activating enzyme 6 (Uba) gene. The construct was electroporated into (C57BL/6 x 129/SvEv)F1-derived BA1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6 mice for at least 5 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Uba6^tm1Whpr
Name: targeted mutation 1, Wade Harper
MGI accession ID: MGI:5509054
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Uba6
Marker name: ubiquitin-like modifier activating enzyme 6
Chromosome: 5
Strain of origin: (C57BL/6NTac x 129S6/SvEvTac)F1
Molecular note: A targeting vector was designed to insert a loxP site upstream of exon 16. A second loxP site, followed by a FRT-flanked neomycin resistance (neo) cassette, was inserted downstream of exon 17.