B6N.129(Cg)-Polgtm1.1Lrsn/Kctt
| Status | Available to order |
| EMMA ID | EM:13213 |
| Citation information | RRID:IMSR_EM:13213 Research Resource Identifiers (RRID) are persistent unique ID numbers assigned to help researchers cite key resources (e.g. antibodies, model organisms and software projects) in the biomedical literature to improve transparency and reproducibility in research. See https://www.rrids.org/ for more information. |
| International strain name | B6N.129(Cg)-Polgtm1.1Lrsn/Kctt |
| Alternative name | Polg tm1Lrsn (PolgA (D257A) loxP, mutator, mtDNA-mutator, PolgA-D257A, PolgA-mut) |
| Strain type | Targeted Mutant Strains : Point mutation |
| Allele/Transgene symbol | Polgtm1.1Lrsn |
| Gene/Transgene symbol | Polg |
Information from provider
| Provider | Nils-Göran Larsson |
| Provider affiliation | Karolinska Institutet |
| Genetic information | The mouse strain is a knock-in mutant expressing a proof-reading-deficient version of the mitochondrial DNA polymerase, PolgA. A mutation has been introduced in exon 3 replacing a critical aspartate residue of the second exonuclease domain with an alanine (D257A). In addition, exon 3 is flanked by loxP sites allowing later excision of exon 3 to generate PolgA knockout mice. A PGK-neo cassette, flanked by FRT sites, was initially introduced to allow selection of targeted ES-cell clones in the production of this mouse. The PGK-neo cassette has been removed by crossing these mice to mice expressing FLP. Further crossings have been done to remove the FLP-expressing transgene. |
| Phenotypic information | Homozygous:Homozygous mice have increased levels of point mutations in the mitochondrial DNA, as well as increased amounts of deleted mtDNA. The increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement.Heterozygous:Heterozygous mice also exhibit increased levels of mutations in the mitochondrial DNA, but show no overt phenotype |
| Breeding history | Males used for sperm freezing are on C57BL/6N background (at least 10 backcrossing generations). |
| References |
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| Homozygous fertile | females only |
| Homozygous viable | yes |
| Homozygous matings required | no |
| Immunocompromised | no |
Information from EMMA
| Archiving centre | Karolinska Institutet, Stockholm, Sweden |
| Animals used for archiving | heterozygous C57BL/6N males |
Disease and phenotype information
Orphanet associated rare diseases, based on orthologous gene matching
- Alpers-Huttenlocher syndrome / Orphanet_726
- Spinocerebellar ataxia with epilepsy / Orphanet_254881
- Autosomal dominant progressive external ophthalmoplegia / Orphanet_254892
- Mitochondrial neurogastrointestinal encephalomyopathy / Orphanet_298
- Recessive mitochondrial ataxia syndrome / Orphanet_94125
- Sensory ataxic neuropathy-dysarthria-ophthalmoparesis syndrome / Orphanet_70595
- Autosomal recessive progressive external ophthalmoplegia / Orphanet_254886
Literature references
- Increased Total mtDNA Copy Number Cures Male Infertility Despite Unaltered mtDNA Mutation Load.;Jiang Min, Kauppila Timo Eino Sakari, Motori Elisa, Li Xinping, Atanassov Ilian, Folz-Donahue Kat, Bonekamp Nina Anna, Albarran-Gutierrez Sara, Stewart James Bruce, Larsson Nils-Göran, ;2017;Cell metabolism;26;429-436.e4; 28768180
- Ultra-deep sequencing of mouse mitochondrial DNA: mutational patterns and their origins.;Ameur Adam, Stewart James B, Freyer Christoph, Hagström Erik, Ingman Max, Larsson Nils-Göran, Gyllensten Ulf, ;2011;PLoS genetics;7;e1002028; 21455489
- Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission.;Freyer Christoph, Cree Lynsey M, Mourier Arnaud, Stewart James B, Koolmeister Camilla, Milenkovic Dusanka, Wai Timothy, Floros Vasileios I, Hagström Erik, Chatzidaki Emmanouella E, Wiesner Rudolf J, Samuels David C, Larsson Nils-Göran, Chinnery Patrick F, ;2012;Nature genetics;44;1282-5; 23042113
- Similar patterns of clonally expanded somatic mtDNA mutations in the colon of heterozygous mtDNA mutator mice and ageing humans.;Baines Holly L, Stewart James B, Stamp Craig, Zupanic Anze, Kirkwood Thomas B L, Larsson Nils-Göran, Turnbull Douglass M, Greaves Laura C, ;2014;Mechanisms of ageing and development;139;22-30; 24915468
- Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice.;Edgar Daniel, Shabalina Irina, Camara Yolanda, Wredenberg Anna, Calvaruso Maria Antonietta, Nijtmans Leo, Nedergaard Jan, Cannon Barbara, Larsson Nils-Göran, Trifunovic Aleksandra, ;2009;Cell metabolism;10;131-8; 19656491
- A Phenotype-Driven Approach to Generate Mouse Models with Pathogenic mtDNA Mutations Causing Mitochondrial Disease.;Kauppila Johanna H K, Baines Holly L, Bratic Ana, Simard Marie-Lune, Freyer Christoph, Mourier Arnaud, Stamp Craig, Filograna Roberta, Larsson Nils-Göran, Greaves Laura C, Stewart James B, ;2016;Cell reports;16;2980-2990; 27626666
- Defects in β-cell Ca2+ dynamics in age-induced diabetes.;Li Luosheng, Trifunovic Aleksandra, Köhler Martin, Wang Yixin, Petrovic Berglund Jelena, Illies Christopher, Juntti-Berggren Lisa, Larsson Nils-Göran, Berggren Per-Olof, ;2014;Diabetes;63;4100-14; 24985350
- High brain lactate is a hallmark of aging and caused by a shift in the lactate dehydrogenase A/B ratio.;Ross Jaime M, Öberg Johanna, Brené Stefan, Coppotelli Giuseppe, Terzioglu Mügen, Pernold Karin, Goiny Michel, Sitnikov Rouslan, Kehr Jan, Trifunovic Aleksandra, Larsson Nils-Göran, Hoffer Barry J, Olson Lars, ;2010;Proceedings of the National Academy of Sciences of the United States of America;107;20087-92; 21041631
- Strong purifying selection in transmission of mammalian mitochondrial DNA.;Stewart James Bruce, Freyer Christoph, Elson Joanna L, Wredenberg Anna, Cansu Zekiye, Trifunovic Aleksandra, Larsson Nils-Göran, ;2008;PLoS biology;6;e10; 18232733
- Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production.;Trifunovic Aleksandra, Hansson Anna, Wredenberg Anna, Rovio Anja T, Dufour Eric, Khvorostov Ivan, Spelbrink Johannes N, Wibom Rolf, Jacobs Howard T, Larsson Nils-Göran, ;2005;Proceedings of the National Academy of Sciences of the United States of America;102;17993-8; 16332961
- Germline mitochondrial DNA mutations aggravate ageing and can impair brain development.;Ross Jaime M, Stewart James B, Hagström Erik, Brené Stefan, Mourier Arnaud, Coppotelli Giuseppe, Freyer Christoph, Lagouge Marie, Hoffer Barry J, Olson Lars, Larsson Nils-Göran, ;2013;Nature;501;412-5; 23965628
- Premature ageing in mice expressing defective mitochondrial DNA polymerase.;Trifunovic Aleksandra, Wredenberg Anna, Falkenberg Maria, Spelbrink Johannes N, Rovio Anja T, Bruder Carl E, Bohlooly-Y Mohammad, Gidlöf Sebastian, Oldfors Anders, Wibom Rolf, Törnell Jan, Jacobs Howard T, Larsson Nils-Göran, ;2004;Nature;429;417-23; 15164064
- Proofreading deficiency in mitochondrial DNA polymerase does not affect total dNTP pools in mouse embryos.;Sharma Sushma, Koolmeister Camilla, Tran Phong, Nilsson Anna Karin, Larsson Nils-Göran, Chabes Andrei, ;2020;Nature metabolism;2;673-675; 32778836
- Somatic mtDNA mutations cause progressive hearing loss in the mouse.;Niu Xianzhi, Trifunovic Aleksandra, Larsson Nils-Göran, Canlon Barbara, ;2007;Experimental cell research;313;3924-34; 17662273