Inactivation of Eα and Eβ expression in inbred and wild mice by multiple distinct mutations, some of which predate speciation within Mus species
Tacchini-Cottier, Fabienne ; Mayer, Werner E. ; Begovich, Ann B. ; Jones, Patricia P.
In: International Immunology, 1995, vol. 7, no. 9, p. 1459-1471
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- The H-2 MHC of mice encodes two functional class II heterodimeric proteins: AαAβ (A) and EαEβ (E). While failure to express the A protein has not been reported, a significant proportion of of H-2 haplotypes In both Inbred and wild mice do not express E proteins. We and others have previously characterized the molecular basis for defective E expression in haplotypes from Mus domestlcus (b, f, q, s, from inbred strains) and Af. castaneus (w17, wild-derived) species, identifying six distinct defects in the genes for Eα or Eβ. In this report we have extended these studies to other E- haplotypes, Including several from f-haplotype-bearlng M. domesticus mice (w29, w57, w302) and one derived from the Asian species M. bactrianus (w301). Analyses at the protein, RNA and DNA levels were employed to Identify the defects in the genes for Ea and Eb. At least one new defect was identified that prevents Eβ expression in a t-associated H-2 haplotypes (w57), bringing the number of distinct mutations causing the Eβ phenotype to seven. Another t-associated haplotype, w302, was found to share the same Eβ defect with mice of the inbred q haplotype and of the w17 haplotype from Af. castaneus, while its Ea gene contains the deletion carried also by the Inbred b and s haplotypes and by a number of wild haplotypes. The mutations in the Ea and Eb genes of the w301 haplotype from M. bactrianus were found to be Identical to those of the Inbred f haplotype. This indicates that the origin of the mutations in the Eb genes of the q, w17 and w302 haplotypes and in the Ea and Eb genes of the f and w301 haplotypes, predated speciation within Mus, thought to have occurred ∼0.35-1 million years ago. Their maintenance in mouse populations suggests that in certain conditions the failure to express EαEβ proteins may be advantageous and selected for