Loci affecting male fertility in hybrids between
Mus macedonicus and C57BL/6
Rosemary W. Elliott, Diane Poslinski, Debra Tabaczynski, Colleen Hohman,
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Carlton and Elm Sts., Buffalo New York, 14263, USA
Received: 10 March 2004 / Accepted: 30 April 2004
hybrids between inbred strains and Mus
macedonicus have very small testes and are sterile.
Cytological analysis of testes shows very few mei-
oses. To determine the genetic basis for this sterility,
(C57BL/6J · Mus macedonics)F
mated to males from C57BL/10J. In about half the
male progeny no meiosis I was observed. About half
of the animals that progressed through meiosis I
showed other indications of low fertility and the
balance appeared fertile. QTL analysis of the progeny
suggested that loci on proximal Chrs 17 and X were
involved in the sterility and a locus on Chr X in
variation of body weight. There is also evidence that
X//Y dissociation of the pseudo-autosomal region
occurs. The QTLs on Chrs X and 17 together account
for about 37% of the variance for testis weight.
Congenic lines B.MAC-X(1-38), and B.MAC-17(1-23)
have been constructed using a modified speed con-
genic approach. Testis tubules from B.MAC-X(1-38)
are narrow and vacuolated. They contain only Sertoli
cells and mitotically dividing spermatogonia. Very
occasionally a meiotic metaphase can be observed,
but no sperm are produced. Homozygous males from
B.MAC-17(1-23) are sterile, producing sperm heads
but no complete sperm.
Several loci affecting hybrid fertility have been re-
ported. Five of these (Hst1, Hst4, Hst5, Hst6, Hst7)
are on the proximal portion of mouse Chromosome
(Chr) 17, and two (Hst3 and Ihtw1) are on Chr X.
Hybrid sterility 1 (Hst1) affects fertility in male F
between inbred strain C57BL/10, carrying Hst1
M. musculus. Similar F
hybrids between C3H, car-
, and M. musculus are fertile (Forejt and
Ivanyi 1974; Trachtulec et al. 1997). Hst4 (Pilder
et al. 1991) and Hst5 and Hst6 (Pilder et al. 1993)
were found by analyzing crosses involving laboratory
strains, M. spretus, and mice carrying t-mutations.
Hst6 has been identified as due to species differences
in axonemal dynein (Samant et al. 1999; Fosella et al.
2000). Hst7 is on proximal Chr 17 (Pilder et al. 1997).
Hst3 is located at the distal end of Chr X (Guenet
et al. 1990). It has been studied in crosses between
M. spretus and C57BL/6 and probably is located in
the pseudo-autosomal region (PAR) (Matsuda et al.
1991). We have reported a locus Ihtw1 (interspecific
hybrid testis weight 1) on proximal Chr X, with a
phenotype that affects both testis weight and hybrid
fertility (Elliott et al. 2001).
Hybrids between C57BL/6J and M. spretus are
sterile. This is probably due to lack of X//Y pairing in
the PAR. Seminiferous tubules from these hybrids
contain spermatocytes, some showing meiotic
metaphase I, although mature sperm are not found.
As with interspecies crosses involving M. spretus,
hybrids between inbred strains and
M. macedonicus are sterile. However, seminiferous
tubules from adult hybrids show almost no meiotic
The studies reported here were designed to de-
termine the genetic basis for this sterility. They
utilized a backcross in which (C57BL/6J · M. mac-
females were mated to C57BL/10J
males. In about half the male progeny no meiotic
metaphase I was observed. About half of the animals
that progressed through meiosis I showed other in-
dications of low fertility and the balance appeared
fertile. A genomewide scan was performed and
quantitative trait loci (QTLs) for testis weight and
body weight have been identified on proximal to
Correspondence to: R.W. Elliott, E-mail: rosemary.elliott@
DOI: 10.1007/s00335-004-2388-y Volume 15, 704–710 (2004) Ó Springer Science+Business Media, Inc. 2004