Journal Article

Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency

Juergen Neesen, Renate Kirschner, Matthias Ochs, Andreas Schmiedl, Barbara Habermann, Christian Mueller, Adolf Friedrich Holstein, Thomas Nuesslein, Ibrahim Adham and Wolfgang Engel

in Human Molecular Genetics

Volume 10, issue 11, pages 1117-1128
Published in print May 2001 | ISSN: 0964-6906
Published online May 2001 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/10.11.1117
Disruption of an inner arm dynein heavy chain gene results in asthenozoospermia and reduced ciliary beat frequency

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Impaired ciliary and flagellar functions resulting in male infertility and recurrent respiratory tract infections are found in patients suffering from primary ciliary dyskinesia (PCD). In most cases, axonemal defects are present, i.e. PCD patients often lack inner and/or outer dynein arms in their sperm tails and cilia, supporting the hypothesis that mutations in dynein genes may cause PCD. However, to date it is unclear whether mutations in dynein heavy chain genes are responsible for impaired flagellar and ciliary motility in mammals. To elucidate the role of the mouse dynein heavy chain 7 (MDHC7) gene, which encodes a component of the inner dynein arm, we have generated mice lacking this dynein heavy chain isoform. Both MDHC7+/– and MDHC7–/– mice are viable and show no malformations; however, homozygous males produce no offspring. In comparison to MDHC7+/– and wild-type mice the spermatozoa of MDHC7–/– mice revealed a dramatic reduced straight line velocity and progressive movement, resulting in the inability of MDHC7-deficient sperm to move from the uterus into the oviduct. Additionally, we measured the beat frequency of tracheal cilia and observed a decrease in the beat frequency of ∼50% in MDHC7–/– mice. The reduction in both ciliary and flagellar motility is not correlated with any gross defects in the axonemal structure. The phenotype of MDHC7–/– mice is similar to that observed in some patients suffering from PCD, and our data strongly suggest that in some patients this disease could be due to mutations in the homologous human gene DNAH1 (HDHC7).

Journal Article.  8529 words.  Illustrated.

Subjects: Genetics and Genomics

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