Unexpected rescue of alpha-synuclein and multimerin1 deletion in C57BL/6JOlaHsd mice by beta-adducin knockout.
Uniform genetic background of inbred mouse strains is essential in experiments with genetically modified mice. In order to assess Add2 (beta-adducin) function, its null mutation was produced in embryonic stem cells derived from 129Sv mouse and the subsequently obtained mouse mutants were backcrossed for 6 generations with C57BL/6JOlaHsd strain. Comparison of brain proteins between mutated and control animals by two-dimensional gels linked to mass spectroscopy analysis showed expression of Snca (alpha-synuclein) in the mutated animals, but unexpectedly not in the control C57BL/6JOlaHsd mice. Comparison between C57BL/6JOlaHsd and C57BL/6NCrl mice confirmed the presence of a deletion encompassing Snca and in addition Mmrn1 (multimerin1) loci in C57BL/6JOlaHsd strain. The segregation of mutated Add2 together with an adjacent part of the chromosome 6 derived from 129Sv mice, rescued the loss of these two genes in knockout mice on C57BL/6JOlaHsd background. The fact that Add2 knockout was compared with the C57BL/6JOlaHsd mouse strain, which is actually a double knockout of Snca and Mmrn1 emphasizes a need for information provided by commercial suppliers and of exact denominations of substrains used in research.
Gajović
Srećko
S
Croatian Institute for Brain Research, School of Medicine, Univeristy of Zagreb, Croatia. srecko.gajovic@hiim.hr
Mitrecić
Dinko
D
Augustincić
Lana
L
Iaconcig
Alessandra
A
Muro
Andrés F
AF
D000818:Animals; D001798:Blood Proteins / Q000172:deficiency / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051844:alpha-Synuclein / Q000172:deficiency / Q000235:genetics*; D000099291:Adducins
D001798:Blood Proteins; D002148:Calmodulin-Binding Proteins; D051844:alpha-Synuclein; D000099291:Adducins; C069282:multimerin