STRAIN-DEPENDENT DEVELOPMENTAL RELAXATION OF IMPRINTING OF AN ENDOGENOUS MOUSE GENE, K(V)LQT1

Genomic imprinting is an epigenetic modification of the gamete or zygo te leading to parental origin-specific differential expression of the two alleles of a gene in somatic cells of the offspring. We previously reported that the human K(V)LQT1 gene is imprinted and disrupted in p atients with germline balanced chromosomal rearrangements and Beckwith -Wiedemann syndrome. In human, the gene is imprinted in most fetal tis sues except the heart, and K(V)LQT1 is part of a 1-Mb cluster of impri nted genes on human chromosome 11p15.5. We sought to determine whether the mouse K(V)1qt1 gene is imprinted, by performing interspecific cro sses of 129/SvEv mice with CAST/E-i (Mus musculus castaneus). We ident ified a transcribed polymorphism that distinguishes the two parental a lleles in F-1 offspring. Examination of embryonic, neonatal, and postn atal tissues revealed that K(V)1qt1 is imprinted in mouse early embryo s, in both female 129 x male CS and female CS x male 129 offspring, wi th preferential expression of the maternal allele, like the human homo logue. Surprisingly, imprinting was developmentally relaxed, and the d evelopmental stage and tissue specificity of relaxation of imprinting was strain-dependent. To our knowledge, this is the first example of a n endogenous gene that shows strain-dependent developmental relaxation of imprinting, (C) 1998 Academic Press.