Mapping and identification of candidate loci responsible for Peromyscus hybrid overgrowth

Abstract

Crosses between two recently diverged rodent species of the genus Peromyscus result in dramatic parent-of-origin effects on growth and development. P. maniculatus females crossed with P. polionotus males yield growth-retarded conceptuses, whereas the reciprocal cross results in overgrowth and lethality. These hybrid effects are particularly pronounced in the placenta. We previously detected linkage to two regions of the genome involved in the overgrowth effects. One locus, termed Peal, is a paternally expressed autosomal locus mapping to a domain whose house mouse equivalent contains several clusters of imprinted genes. The other locus, termed Mexl, maps to a gene-poor region of the X chromosome. Here we use an advanced intercross line to verify and narrow the regions of linkage and identify candidate genes for Mexl and Peal. While we have previously shown that Mexl affects both pre-and postnatal growth, we show here that Peal affects only prenatal growth. Utilizing criteria such as mutant phenotypes and allelic expression, we identify the loci encoding the homeobox protein Esx1 and the zinc-finger protein Pw1/Peg3 as candidates. Both loci exhibit expression changes in the hybrids.

Fig. 1.

Distribution of the maternal Esx1 alleles in the AIL × BW crosses. Vertical axis represents number of animals, horizontal axis indicates placental weight in grams.

Fig. 2.

Distribution of the paternal Pw1/Peg3 alleles in the PO × AIL crosses. Vertical axis represents number of animals, horizontal axis indicates placental weight in grams.

Fig. 3.

Distribution of sex and weight in the PO × F1 cross at postnatal day 45. Vertical axis represents number of animals, horizontal axis indicates body weight in grams. Parental mean body weights ( ± one standard deviation) are as follows : PO♀ = 15.3 ± 1.2, PO♂ = 12.4 ± 0.4, BW♀ = 15.5 ± 1.6, BW♂ = 17.4 ± 1.4.

Fig. 4.

Quantitative PCR analysis of Esx1 expression. Each indicated genotype-tissue type combination represents multiple samples, with the exception of testis. Standard error bars are indicated.

Fig. 5.

Quantitative PCR analysis of Pw1/Peg3 expression. Each indicated genotype-tissue type combination represents multiple samples, with the exception of testis. Standard error bars are indicated.