Induction of gene mutations in mice: The multiple endpoint approach

Ehling, U.H.; Charles, Daniel J.; Favor, Jack; Graw, Jochen; Kratochvílová, Jana; Neuhäuser-Klaus, A.; Pretsch, Walter

doi:10.1016/0027-5107(85)90136-8

Cited by 93 publications

(21 citation statements)

References 13 publications

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“…A systematic approach to collect mouse cataract mutants was initiated more than 30 years ago by Kratochvilova and Ehling (1979), when they used paternal treatment of germ cells by X-rays and screened for cataracts in the offspring. The method was extended to the use of ethylnitrosourea (ENU) as a mutagenic agent (Ehling et al 1985) and is now continued world wide as a valuable tool for a broad variety of disorders (Hrabé de Angelis et al 2000;Clark et al 2004;Barbaric et al 2007;Takahasi et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Mouse models of cataract

Graw

2009

J Genet

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Much of our knowledge about the function of genes in cataracts has been derived from the molecular analysis of spontaneous or induced mutations in the mouse. Mutations affecting the mouse lens can be identified easily by visual inspection, and a remarkable number of mutant lines have been characterized. In contrast to humans, most of the genetic mouse cataract models suffer from congenital cataracts, and only a few develop cataracts in old age. Therefore, the mouse cataract models contributed rather to the understanding of lens development than to the ageing process taking place in the lens. A prerequisite for molecular analysis is the chromosomal localization of the gene. In this review, several mouse models will be discussed with emphasis on the underlying genetic basis rather than the morphological features as exemplified by the following: (i) the most frequent mutations in congenital cataracts affect genes coding for gamma-crystallins (gene symbol: Cryg); (ii) some postnatal, progressive cataracts have been characterized by mutations in the beta-crystallin encoding genes (Cryb); (iii) mutations in genes coding for membrane proteins like MIP or connexins lead to congenital cataracts; (iv) mutations in genes coding for transcription factors such as FoxE3, Maf, Sox1, and Six5 cause cataracts; (v) mouse models suffering from hereditary age-related cataracts (e.g. Emory cataract) have not yet been characterized genetically. In conclusion, a broad variety of hereditary congenital cataracts are well understood at the molecular level. Further, expression patterns of the affected genes in several other tissues and organs outside the eye, is making it increasingly clear that isolated cataracts are the exception rather than the rule. By further understanding the pleiotropic effects of these genes, we might recognize cataracts as an easily visible biomarker for a number of systemic syndromes.

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Section: Introductionmentioning

confidence: 99%

Mouse models of cataract

Graw

2009

J Genet

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“…Male C3HeB/FeJ mice were treated with ethylnitrosourea (ENU; 160 mg/kg) at the age of 10 weeks according to Ehling et al (1985) and mated to untreated female C3HeB/FeJ mice. Mice were kept under specific pathogen-free conditions at the GSF and monitored within the ENU mouse mutagenesis screen project (Hrabé de Angelis and Balling, 1998 Phenotypic characterization.…”

Section: Methodsmentioning

confidence: 99%

Mutation in the βA3/A1-Crystallin Encoding Gene Cryba1 Causes a Dominant Cataract in the Mouse

et al. 1999

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“…Their mt varies widely, and the question raised of how representative thesc for the entire genome. To incr number of tested loci by a factor c multiple end point approach was d by Ehling et al (30). In this appr progeny are screened for the 7 recessive loci and for 23 loci co protein-charge changes (22)(23)(24) for enzyme activity alterations ( about 30 loci coding for dominan mutations (21).…”

Section: Present Methods Of Germ Cell Studiesmentioning

confidence: 99%