Genetics, Vol. 166, 913-924, February 2004, Copyright © 2004

Hybrid Breakdown Caused by Substitution of the X Chromosome Between Two Mouse Subspecies

Ayako Okaa,b, Akihiko Mitaa, Noriko Sakurai-Yamatania, Hiromi Yamamotoa, Nobuo Takagic, Toshiyuki Takano-Shimizud, Kiyotaka Toshimorie, Kazuo Moriwakif, and Toshihiko Shiroishia,b
a Mammalian Genetics Laboratory, National Institute of Genetics, Mishima, Shizuoka-ken 411-8540, Japan,
b Graduate University for Advanced Studies, Hayama, Kanagawa-ken 240-0193, Japan,
c Division of Bioscience, Graduate School of Environmental Earth Science, Hokkaido University, Kita-ku, Sapporo 060-0810, Japan,
d Department of Population Genetics, National Institute of Genetics, Mishima, Shizuoka-ken 411-8540, Japan,
e Department of Anatomy and Developmental Biology (G1), Graduate School of Medicine, Chiba University, Chiba City, 260-8670, Japan
f RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan

Corresponding author: Toshihiko Shiroishi, National Institute of Genetics, Yata 1111, Mishima, Shizuoka-ken 411-8540, Japan., tshirois{at}lab.nig.ac.jp (E-mail)

Communicating editor: C. KOZAK

Hybrid breakdown is a type of reproductive failure that appears after the F2 generation of crosses between different species or subspecies. It is caused by incompatibility between interacting genes. Genetic analysis of hybrid breakdown, particularly in higher animals, has been hampered by its complex nature (i.e., it involves more than two genes, and the phenotype is recessive). We studied hybrid breakdown using a new consomic strain, C57BL/6J-XMSM, in which the X chromosome of C57BL/6J (derived mostly from Mus musculus domesticus) is substituted by the X chromosome of the MSM/Ms strain (M. m. molossinus). Males of this consomic strain are sterile, whereas F1 hybrids between C57BL/6J and MSM/Ms are completely fertile. The C57BL/6J-XMSM males showed reduced testis weight with variable defects in spermatogenesis and abnormal sperm head morphology. We conducted quantitative trait locus (QTL) analysis for these traits to map the X-linked genetic factors responsible for the sterility. This analysis successfully detected at least three distinct loci for the sperm head morphology and one for the testis weight. This study revealed that incompatibility of interactions of X-linked gene(s) with autosomal and/or Y-linked gene(s) causes the hybrid breakdown between the genetically distant C57BL/6J and MSM/Ms strains.




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