Next-generation gene targeting in the mouse for functional genomics

Gondo, Yoichi; Fukumura, Ryutaro; Murata, Takuya; Makino, Seiya

doi:10.5483/bmbrep.2009.42.6.315

Cited by 37 publications

(17 citation statements)

References 57 publications

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“…In our study, mutator mice bred for 20 generations gave rise to 6335 SNVs (the sum of the numbers of heterozygous and homozygous variants). This is much higher than the estimated number of mutations induced by ENU treatment (2105 SNVs) (Gondo et al 2009) or the number of de novo SNVs predicted to distinguish the original C57 mouse stock (Russell 1978) from the C57BL/6J strain currently distributed by Jackson Laboratory (3292 SNVs, calculated using our estimated mutation rate and the known generation number, F226). Considering that our comparison of the variant data between the mutC/mutD lines and the mutE line indicated that the frequency of recurrent mutations in the mutator mice was low (details in Supplemental Information), the long-term breeding of mutator mice is a promising method for enhancing mutagenesis across the entire genome.…”

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confidence: 66%

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Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice

et al. 2015

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The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates. We estimated the base-substitution mutation rate to be 5.4 × 10 −9 (95% confidence interval = 4.6 × 10 −9 -6.5 × 10 −9 ) per nucleotide per generation in C57BL/6 laboratory mice, about half the rate reported in humans. The mutation rate in mutator mice was 17 times that in wild-type mice. Abnormal phenotypes were 4.1-fold more frequent in the mutator lines than in the wild-type lines. After several generations, the mutator mice reproduced at substantially lower rates than the controls, exhibiting low pregnancy rates, lower survival rates, and smaller litter sizes, and many of the breeding lines died out. These results provide fundamental information about mouse genetics and reveal the impact of germline mutation rates on phenotypes in a mammalian population.

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confidence: 66%

“…) of wild-type mice and the known rate (8.0 × 10 −7 ) of mice treated with the widely used chemical mu- Table 2; Keays et al 2006;Gondo et al 2009). …”

Section: Germline Mutation Rates In Micementioning

confidence: 99%

Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice

et al. 2015

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“…43,44 Currently, there are at least 20 ENU consortiums around the world. 45 Such programs have revealed many critical genes for human diseases, including male infertility. [46][47][48][49] …”

Section: Mouse Models In Male Fertility Research D Jamsai and Mk O'brmentioning

confidence: 99%

Mouse models in male fertility research

Jamsai¹,

O'Bryan²

2010

Asian J Androl

113

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Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options. Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population, this approach has progressed slowly due to the limitations described herein. Given the complexity of male fertility, the entire process cannot be modeled in vitro. As such, animal models, in particular mouse models, provide a valuable alternative for gene identification and experimentation. Since the introduction of molecular biology and recent advances in animal model production, there has been a substantial acceleration in the identification and characterization of genes associated with many diseases, including infertility. Three major types of mouse models are commonly used in biomedical research, including knockout/knockin/gene-trapped, transgenic and chemical-induced point mutant mice. Using these mouse models, over 400 genes essential for male fertility have been revealed. It has, however, been estimated that thousands of genes are involved in the regulation of the complex process of male fertility, as many such genes remain to be characterized. The current review is by no means a comprehensive list of these mouse models, rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.

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“…Although the in vitro models have helped us to understand molecular pathways of cancer, they don't model adequately the spontaneous human tumours because of limitations like selective transformation with a selection of certain gene sets, morphologic characters, and functions (MacLeod et al, 1999;Masters, 2002). The mouse has been the most frequent model for genetic studies in mammals with advantages like small size, average lifespan of about 2 years, short gestation period and inexpensiveness in contrast to other mammals but it has got significant limitations when used to study complex human diseases (Paigen, 1995;Strauch et al, 2003;Gondo et al, 2009;Seok et al, 2013). There are genetic, immunological and cellular differences between human and mice which make it a poor model for cancer study (Schuh, 2004).…”

Section: Introductionmentioning

confidence: 99%

Comparative oncology: Integrating human and veterinary medicine

Sultan

Ganaie²

2018

Open Vet J.

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Cancer constitutes the major health problem both in human and veterinary medicine. Comparative oncology as an integrative approach offers to learn more about naturally occurring cancers across different species. Canine models have many advantages as they experience spontaneous disease, have many genes similar to human genes, five to seven-fold accelerated ageing compared to humans, respond to treatments similarly as humans do and health care levels second only to humans. Also, the clinical trials in canines could generate more robust data, as their spontaneous nature mimics real-life situations and could be translated to humans.

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Next-generation gene targeting in the mouse for functional genomics

Cited by 37 publications

References 57 publications

Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice

Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice

Mouse models in male fertility research

Comparative oncology: Integrating human and veterinary medicine

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