Distorted Mendelian transmission as a function of genetic background in Rai1-haploinsufficient mice

European Journal of Medical Genetics
Santhosh Girirajan, Sarah Elsea

Abstract

The retinoic acid induced 1 gene (RAI1) is the primary causative gene for Smith-Magenis syndrome (SMS). Chromosomal deletion encompassing RAI1 or mutation in RAI1 is responsible for the majority of SMS features. Mouse models with targeted disruption of Rai1 have recapitulated overt SMS phenotypes, including craniofacial abnormalities, obesity, and neurobehavioral anomalies. Penetrance and expressivity of most phenotypes in mice were incomplete due to the mixed genetic background in which they were created. While increased penetrance of craniofacial phenotypes was observed in relatively homogeneous backgrounds, the effect of Rai1 haploinsufficiency on breeding outcome and fitness has not been studied. We analyzed mating results of Rai1+/- mice in a pure C57BL/6J background (>or=N10 generations). A significant distortion (P<0.05) of Mendelian transmission ratio with skewing against Rai1+/- mice was observed. Consequently, a decreased number of Rai1+/- pups and no Rai1-/- pups were obtained from all the breeding pairs. The decreased yield of Rai1+/- pups precluded penetrance studies of other phenotypes in these mice. However, when Rai1+/- alleles were transferred to a slightly variable (approximately 1% 129/approximately 99% C57BL...Continue Reading

References

Mar 4, 2000·Nature Genetics·J H NadeauE S Lander
Apr 18, 2000·Human Molecular Genetics·L M Tarantino, M Bucan
Mar 21, 2001·Nature Reviews. Genetics·J H Nadeau
Mar 25, 2005·Journal of Medical Genetics·S GirirajanS H Elsea
Jul 18, 2006·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Santhosh GirirajanSarah H Elsea
Jan 31, 2008·European Journal of Human Genetics : EJHG·Sarah H Elsea, Santhosh Girirajan
Feb 21, 2008·European Journal of Human Genetics : EJHG·Santhosh GirirajanSarah H Elsea

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