Spam1-associated transmission ratio distortion in mice: Elucidating the mechanism
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Spam1-associated transmission ratio distortion in mice: Elucidating the mechanism Patricia A Martin-DeLeon*1, Hong Zhang1, Carlos R Morales2, Yutong Zhao1, Michelle Rulon1, Barry L Barnoski3, Hong Chen1 and Deni S Galileo1 Address: 1Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA, 2Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada and 3Department of Genetics, Thomas Jefferson University, Philadelphia, PA, USA Email: Patricia A Martin-DeLeon* - [email protected]; Hong Zhang - [email protected]; Carlos R Morales - [email protected]; Yutong Zhao - [email protected]; Michelle Rulon - [email protected]; Barry L Barnoski - [email protected]; Hong Chen - [email protected]; Deni S Galileo - [email protected] * Corresponding author
Published: 10 August 2005 Reproductive Biology and Endocrinology 2005, 3:32 32
doi:10.1186/1477-7827-3-
Received: 02 May 2005 Accepted: 10 August 2005
This article is available from: http://www.rbej.com/content/3/1/32 © 2005 Martin-DeLeon et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: While transmission ratio distortion, TRD, (a deviation from Mendelian ratio) is extensive in humans and well-documented in mice, the underlying mechanisms are unknown. Our earlier studies on carriers of spontaneous mutations of mouse Sperm Adhesion Molecule 1 (Spam1) suggested that TRD results from biochemically different sperm, due to a lack of transcript sharing through the intercellular cytoplasmic bridges of spermatids. These bridges usually allow transcript sharing among genetically different spermatids which develop into biochemically and functionally equivalent sperm. Objectives: The goals of the study were to provide support for the lack of sharing (LOS) hypothesis, using transgene and null carriers of Spam1, and to determine the mechanism of Spam1-associated TRD. Methods: Carriers of Spam1-Hyal5 BAC transgenes were mated with wild-type female mice and the progeny analyzed for TRD by PCR genotyping. Sperm from transgene and Spam1 null carriers were analyzed using flow cytometry and immunocytochemistry to detect quantities of Spam1 and/or Hyal5. Transgene-bearing sperm with Spam1 overexpression were detected by fluorescence in situ hybridization. In wild-type animals, EM studies of in situ transcript hybridization of testis sections and Northern analysis of biochemically fractionated testicular RNA were performed to localize Spam1 transcript. Finally, AU-rich motifs identified in the 3' UTR of Spam1 RNA were assayed by UV cross-linking to determine their ability to interact with testicular RNA binding proteins. Results: The Tg8 line of transgene carriers had a significant (P < 0.001) TRD, due to reduced fert
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