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Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice.

Yuan S, Oliver D, Schuster A, Zheng H, Yan W - Sci Rep (2015)

Bottom Line: Paramutations result from interactions between two alleles at a single locus, whereby one induces a heritable change in the other.Although common in plants, paramutations are rarely studied in animals.Mechanistic insights of ETI will help us understand how organisms establish new heritable epigenetic states during development, or in times of environmental or nutritional stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

ABSTRACT
Paramutations result from interactions between two alleles at a single locus, whereby one induces a heritable change in the other. Although common in plants, paramutations are rarely studied in animals. Here, we report a new paramutation mouse model, in which the paramutant allele was induced by an insertional mutation and displayed the "white-tail-tip" (WTT) phenotype. The paramutation phenotype could be transmitted across multiple generations, and the breeding scheme (intercrossing vs. outcrossing) drastically affected the transmission efficiency. Paternal (i.e., sperm-borne) RNAs isolated from paramutant mice could induce the paramutation phenotype, which, however, failed to be transmitted to subsequent generations. Maternal miRNAs and piRNAs appeared to have an inhibitory effect on the efficiency of germline transmission of the paramutation. This paramutation mouse model represents an important tool for dissecting the underlying mechanism, which should be applicable to the phenomenon of epigenetic transgenerational inheritance (ETI) in general. Mechanistic insights of ETI will help us understand how organisms establish new heritable epigenetic states during development, or in times of environmental or nutritional stress.

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The “white-tail-tip” phenotype is not unique to Kit paramutant mice, as demonstrated by different breeding schemes using normal wild-type C57BL/6J mice.(A) Incidence of the “white-tail-tip” (WTT) phenotype among offspring form WT BTT parents. (B) Incidence of the WTT phenotype among offspring derived from WT BTT fathers and WT WTT mothers. (C) Incidence of the WTT phenotype among offspring derived from WT WTT fathers and WT BTT mothers. (D) Incidence of the WTT phenotype among offspring derived from WT WTT parents. “n” denotes the total number of offspring observed in each of the four mating schemes (A–D).
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f2: The “white-tail-tip” phenotype is not unique to Kit paramutant mice, as demonstrated by different breeding schemes using normal wild-type C57BL/6J mice.(A) Incidence of the “white-tail-tip” (WTT) phenotype among offspring form WT BTT parents. (B) Incidence of the WTT phenotype among offspring derived from WT BTT fathers and WT WTT mothers. (C) Incidence of the WTT phenotype among offspring derived from WT WTT fathers and WT BTT mothers. (D) Incidence of the WTT phenotype among offspring derived from WT WTT parents. “n” denotes the total number of offspring observed in each of the four mating schemes (A–D).

Mentions: The WTT phenotype in Kittm1Alf-induced paramutant mice has been questioned because normal WT laboratory mice of different strains (including C57BL/6J) display WTTs32. Indeed, we noticed that many of our pure WT mice, which were on either C57BL/6J or 129/SvEv (Fig. 1B, right panel) background and were totally unrelated to the KitcopGFP line, also displayed WTTs albeit at a much lower incidence. To determine the baseline incidence of the WTT phenotype among WT C57BL/6J mice, we set up four types of breeding pairs between WT males and females that were completely unrelated to the KitcopGFP line, including WT BTT males mated with WT BTT (Fig. 2A) or WT WTT (Fig. 2B) females, and WT WTT males mated with WT BTT (Fig. 2C) or WT WTT (Fig. 2D) females. ~30% of the F1 WT progeny produced by WT BTT mating pairs displayed WTTs (Fig. 2A), whereas WTTs were observed in ~38–40% of the F1 WT offspring derived from the breeding pairs with one of the parents that were WTT-positive (Fig. 2B–D). These data suggest that ~30–40% of WT laboratory C57BL/6J mice display WTTs.


Breeding scheme and maternal small RNAs affect the efficiency of transgenerational inheritance of a paramutation in mice.

Yuan S, Oliver D, Schuster A, Zheng H, Yan W - Sci Rep (2015)

The “white-tail-tip” phenotype is not unique to Kit paramutant mice, as demonstrated by different breeding schemes using normal wild-type C57BL/6J mice.(A) Incidence of the “white-tail-tip” (WTT) phenotype among offspring form WT BTT parents. (B) Incidence of the WTT phenotype among offspring derived from WT BTT fathers and WT WTT mothers. (C) Incidence of the WTT phenotype among offspring derived from WT WTT fathers and WT BTT mothers. (D) Incidence of the WTT phenotype among offspring derived from WT WTT parents. “n” denotes the total number of offspring observed in each of the four mating schemes (A–D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4363887&req=5

f2: The “white-tail-tip” phenotype is not unique to Kit paramutant mice, as demonstrated by different breeding schemes using normal wild-type C57BL/6J mice.(A) Incidence of the “white-tail-tip” (WTT) phenotype among offspring form WT BTT parents. (B) Incidence of the WTT phenotype among offspring derived from WT BTT fathers and WT WTT mothers. (C) Incidence of the WTT phenotype among offspring derived from WT WTT fathers and WT BTT mothers. (D) Incidence of the WTT phenotype among offspring derived from WT WTT parents. “n” denotes the total number of offspring observed in each of the four mating schemes (A–D).
Mentions: The WTT phenotype in Kittm1Alf-induced paramutant mice has been questioned because normal WT laboratory mice of different strains (including C57BL/6J) display WTTs32. Indeed, we noticed that many of our pure WT mice, which were on either C57BL/6J or 129/SvEv (Fig. 1B, right panel) background and were totally unrelated to the KitcopGFP line, also displayed WTTs albeit at a much lower incidence. To determine the baseline incidence of the WTT phenotype among WT C57BL/6J mice, we set up four types of breeding pairs between WT males and females that were completely unrelated to the KitcopGFP line, including WT BTT males mated with WT BTT (Fig. 2A) or WT WTT (Fig. 2B) females, and WT WTT males mated with WT BTT (Fig. 2C) or WT WTT (Fig. 2D) females. ~30% of the F1 WT progeny produced by WT BTT mating pairs displayed WTTs (Fig. 2A), whereas WTTs were observed in ~38–40% of the F1 WT offspring derived from the breeding pairs with one of the parents that were WTT-positive (Fig. 2B–D). These data suggest that ~30–40% of WT laboratory C57BL/6J mice display WTTs.

Bottom Line: Paramutations result from interactions between two alleles at a single locus, whereby one induces a heritable change in the other.Although common in plants, paramutations are rarely studied in animals.Mechanistic insights of ETI will help us understand how organisms establish new heritable epigenetic states during development, or in times of environmental or nutritional stress.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

ABSTRACT
Paramutations result from interactions between two alleles at a single locus, whereby one induces a heritable change in the other. Although common in plants, paramutations are rarely studied in animals. Here, we report a new paramutation mouse model, in which the paramutant allele was induced by an insertional mutation and displayed the "white-tail-tip" (WTT) phenotype. The paramutation phenotype could be transmitted across multiple generations, and the breeding scheme (intercrossing vs. outcrossing) drastically affected the transmission efficiency. Paternal (i.e., sperm-borne) RNAs isolated from paramutant mice could induce the paramutation phenotype, which, however, failed to be transmitted to subsequent generations. Maternal miRNAs and piRNAs appeared to have an inhibitory effect on the efficiency of germline transmission of the paramutation. This paramutation mouse model represents an important tool for dissecting the underlying mechanism, which should be applicable to the phenomenon of epigenetic transgenerational inheritance (ETI) in general. Mechanistic insights of ETI will help us understand how organisms establish new heritable epigenetic states during development, or in times of environmental or nutritional stress.

Show MeSH
Related in: MedlinePlus