Journal Article

A retroviral Gene Trap Insertion into the Histone 3.3A Gene Causes Partial Neonatal Lethality, Stunted Growth, Neuromuscular Deficits and Male Sub-fertility in Transgenic Mice

Christine Couldrey, Mark B.L. Carlton, Patrick M. Nolan, William H. Colledge and Martin J. Evans

in Human Molecular Genetics

Volume 8, issue 13, pages 2489-2495
Published in print December 1999 | ISSN: 0964-6906
Published online December 1999 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/8.13.2489
A retroviral Gene Trap Insertion into the Histone 3.3A Gene Causes Partial Neonatal Lethality, Stunted Growth, Neuromuscular Deficits and Male Sub-fertility in Transgenic Mice

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Spermatogenesis is a complex developmental process involving cell division and differentiation. Approximately half of all sterile males have defects in spermatogenesis or sperm function. An insight into the molecular control points regulating this process might help in treating male infertility. Gene trapping in embryonic stem cells and the generation of transgenic mice represents one route to identify gene sex pressed during spermatogenesis. The trapped gene is tagged with a lacZ reporter gene so that the expression pattern of the gene can be visualized by staining for β-galactosidase activity. We have screened transgenic mouse lines for expression of trapped genes in the gonads. One such trap event was shown to be in the replacement histone 3.3A gene (H3.3A). This gene was expressed ubiquitously during embryonic development until 13.5 days post-coitum and in the adult heart, kidney, brain, testes and ovaries. This mutation resulted in postnatal death of 50% of homozygous mutants. Surviving mutants displayed reduced growth rates when competing with wild-type siblings for food. Mutant mice also had a neuro-muscular deficit and males displayed reduced copulatory activity. When copulations did occur, these resulted in very few pregnancies, suggesting that mutations in the H3.3A gene may contribute to some cases of impaired fertility in man.

Journal Article.  4590 words.  Illustrated.

Subjects: Genetics and Genomics

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