N-ethyl-N-nitrosourea mutagenesis produced a small number of mice with altered plasma electrolyte levels

被引:2
作者
Aigner, Bernhard [1 ,2 ]
Rathkolb, Birgit [1 ,2 ]
Klempt, Martina [1 ,2 ]
Wagner, Sibylle [3 ,4 ]
Michel, Dian [3 ,4 ]
de Angelis, Martin Hrabe [3 ,4 ]
Wolf, Eckhard [1 ,2 ]
机构
[1] Ludwig Maximilians Univ Munchen, Gene Ctr, Dept Vet Sci, Chair Mol Anim Breeding & Biotechnol, Munich, Germany
[2] Ludwig Maximilians Univ Munchen, Gene Ctr, Lab Funct Genome Anal LAFUGA, Munich, Germany
[3] Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany
[4] Tech Univ Munich, Chair Expt Genet, Freising Weihenstephan, Germany
关键词
INDUCED MOUSE MUTANTS; PHENOTYPE-DRIVEN; ENU MUTAGENESIS; DISEASE-MODELS; GENOME-WIDE; HYPOPHOSPHATEMIA; MUTATION; RICKETS; PROJECT; SCREEN;
D O I
10.1186/1423-0127-16-53
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Clinical chemical blood analysis including plasma electrolytes is routinely carried out for the diagnosis of various organ diseases. Phenotype-driven N-ethyl-N-nitrosourea (ENU) mouse mutagenesis projects used plasma electrolytes as parameters for the generation of novel animal models for human diseases. Methods: Here, we retrospectively evaluated the use of the plasma electrolytes calcium, chloride, inorganic phosphorus, potassium and sodium in the Munich ENU mouse mutagenesis project where clinical chemical blood analysis was carried out on more than 20,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in various plasma parameter levels. Results: We identified a small number of animals consistently exhibiting altered plasma electrolyte values. Transmission of the phenotypic deviations to the subsequent generations led to the successful establishment of mutant lines for the parameters calcium and potassium. Published data from other phenotype-driven ENU projects also included only a small number of mutant lines which were generated according to altered plasma electrolyte levels. Conclusion: Thus, use of plasma electrolytes detected few mouse mutants in ENU projects compared to other clinical chemical blood parameters.
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页数:7
相关论文
共 22 条
[1]   Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects [J].
Aigner, Bernhard ;
Rathkolb, Birgit ;
Herbach, Nadja ;
de Angelis, Martin Hrabe ;
Wanke, Ruediger ;
Wolf, Eckhard .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2008, 294 (02) :E232-E240
[2]   Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models [J].
Aigner, Bernhard ;
Rathkolb, Birgit ;
Herbach, Nadja ;
Kemter, Elisabeth ;
Schessl, Christina ;
Klaften, Matthias ;
Klempt, Martina ;
de Angelis, Martin Hrabe ;
Wanke, Rudiger ;
Wolf, Eckhard .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2007, 292 (05) :F1560-F1567
[3]   Generation of N-ethyl-N-nitrosourea-induced mouse mutants with deviations in plasma enzyme activities as novel organ-specific disease models [J].
Aigner, Bernhard ;
Rathkolb, Birgit ;
Klaften, Matthias ;
Sedlmeier, Reinhard ;
Klempt, Martina ;
Wagner, Sibylle ;
Michel, Dian ;
Mayer, Ulrike ;
Klopstock, Thomas ;
de Angelis, Martin Hrabe ;
Wolf, Eckhard .
EXPERIMENTAL PHYSIOLOGY, 2009, 94 (04) :412-421
[4]   Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse [J].
Barbaric, Ivana ;
Wells, Sara ;
Russ, Andreas ;
Dear, T. Neil .
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 2007, 48 (02) :124-142
[5]   An ethyl-nitrosourea-induced point mutation in Phex causes exon skipping, X-linked hypophosphatemia, and rickets [J].
Carpinelli, MR ;
Wicks, IP ;
Sims, NA ;
O'Donnell, K ;
Hanzinikolas, K ;
Burt, R ;
Foote, SJ ;
Bahlo, M ;
Alexander, WS ;
Hilton, DJ .
AMERICAN JOURNAL OF PATHOLOGY, 2002, 161 (05) :1925-1933
[6]   Genetic background determines metabolic phenotypes in the mouse [J].
Champy, Marie-France ;
Selloum, Mohammed ;
Zeitler, Valirie ;
Caradec, Claudia ;
Jung, Barbara ;
Rousseau, Stephane ;
Pouilly, Laurent ;
Sorg, Tania ;
Auwerx, Johan .
MAMMALIAN GENOME, 2008, 19 (05) :318-331
[7]   N-ethyl-N-nitrosourea mutagenesis:: Boarding the mouse mutant express [J].
Cordes, SP .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2005, 69 (03) :426-+
[8]   Genome-wide, large-scale production of mutant mice by ENU mutagenesis [J].
de Angelis, MH ;
Flaswinkel, H ;
Fuchs, H ;
Rathkolb, B ;
Soewarto, D ;
Marschall, S ;
Heffner, S ;
Pargent, W ;
Wuensch, K ;
Jung, M ;
Reis, A ;
Richter, T ;
Alessandrini, F ;
Jakob, T ;
Fuchs, E ;
Kolb, H ;
Kremmer, E ;
Schaeble, K ;
Rollinski, B ;
Roscher, A ;
Peters, C ;
Meitinger, T ;
Strom, T ;
Steckler, T ;
Holsboer, F ;
Klopstock, T ;
Gekeler, F ;
Schindewolf, C ;
Jung, T ;
Avraham, K ;
Behrendt, H ;
Ring, J ;
Zimmer, A ;
Schughart, K ;
Pfeffer, K ;
Wolf, E ;
Balling, R .
NATURE GENETICS, 2000, 25 (04) :444-447
[9]  
DEANGELIS MH, 2007, MOUSE BIOMEDICAL RES, V1, P225
[10]   Introducing the German Mouse Clinic:: open access platform for standardized phenotyping [J].
Gailus-Durner, V ;
Fuchs, H ;
Becker, L ;
Bolle, I ;
Brielmeier, M ;
Calzada-Wack, J ;
Evert, R ;
Ehrhardt, N ;
Dalkel, C ;
Franz, TJ ;
Grundner-Culemann, E ;
Hammelbacher, S ;
Hölter, SM ;
Hötzlwimmer, G ;
Horsch, M ;
Javaheri, A ;
Kataydjiev, SV ;
Klempt, M ;
Kling, E ;
Kunder, S ;
Lengger, C ;
Lisse, T ;
Mijalski, T ;
Naton, B ;
Pedersen, V ;
Prehn, C ;
Przemeck, G ;
Racz, I ;
Reinhard, C ;
Reitmeir, P ;
Schneider, I ;
Schrewe, A ;
Steinkamp, R ;
Zybill, C ;
Adamski, J ;
Beckers, J ;
Behrendt, H ;
Favor, J ;
Graw, J ;
Heldmaier, G ;
Höfer, H ;
Ivandic, B ;
Katus, H ;
Kirchhof, P ;
Kiingenspor, M ;
Kopstock, T ;
Lengeling, A ;
Mfitier, W ;
Ohl, F ;
Ollert, M .
NATURE METHODS, 2005, 2 (06) :403-404