title: Infertility associated with meiotic failure in the tremor rat (tm/tm) is caused by the deletion of spermatogenesis associated 22.
abstract: The tremor rat is an autosomal recessive mutant exhibiting sterility with gonadal hypoplasia in both sexes. The causative mutation tremor (tm) is known as a genomic deletion spanning >200 kb in Chr 10q24. Spermatogenesis associated 22 (Spata22) has been shown to be a vertebrate-specific gene essential for the progression of meiosis through prophase I and completion of chromosome synapsis and meiotic recombination using a mouse repro42 mutant carrying an N-ethyl-N-nitrosourea (ENU)-induced nonsense mutation in Spata22. In this study, we show that Spata22 was identified as the gene responsible for the failure of gametogenesis to progress beyond meiosis I in tm homozygous rats by a transgenic rescue experiment. Meiosis was arrested during prophase I in the mutant testis. Precise mapping of the breakage point revealed that the deleted genomic region spanned approximately 240 kb and comprised at least 13 genes, including Spata22. Rat Spata22 was predominantly expressed in the testis, and its transcription increased with the first wave of spermatogenesis, as seen in the mouse ortholog. These results suggest that Spata22 may play an important role in meiotic prophase I in rats, as seen in mice, and that the tm homozygous rat may be useful for investigating the physiological function of Spata22, as an experimental system for clarifying the effect of a null mutation, and may be an animal model for studying the pathogenesis and treatment of infertility caused by impaired meiosis.
authors.affiliation: Division of Bioscience, Graduate School of Environmental Earth Science, Hokkaido University, North 10 West 8, Kita-ku, Sapporo 060-0810, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishishita
authors.forename: Toshihide
authors.initials: T
authors.lastname: Inui
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Tadao
authors.initials: T
authors.lastname: Serikawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kitada
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D018389:Codon, Nonsense; D005260:Female; D005718:Gametogenesis / Q000235:genetics*; D017353:Gene Deletion; D006720:Homozygote; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D051381:Rats; D011921:Rats, Inbred WKY; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014202:Tremor / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; C573338:SPATA22 protein, mouse
references.citation: Biol Reprod. 2012 Feb 29;86(2):45
references.pmid: 22011390
references.citation: Biochim Biophys Acta. 2008 Jan;1779(1):3-16
references.pmid: 18078840
references.citation: J Med Genet. 2001 Mar;38(3):E9
references.pmid: 11238686
references.citation: Hum Mutat. 2008 Apr;29(4):532-6
references.pmid: 18186520
references.citation: Cytogenet Cell Genet. 1981;29(3):166-75
references.pmid: 7226897
references.citation: J Androl. 2005 Mar-Apr;26(2):189-96
references.pmid: 15713825
references.citation: Mol Genet Metab. 2010 Feb;99(2):184-5
references.pmid: 19932039
references.citation: Science. 2005 Mar 4;307(5714):1468-72
references.pmid: 15746429
references.citation: Mol Cell. 2000 Nov;6(5):975-87
references.pmid: 11106738
references.citation: Mol Hum Reprod. 2002 Jun;8(6):511-7
references.pmid: 12029067
references.citation: Biol Reprod. 1998 Jul;59(1):84-92
references.pmid: 9674997
references.citation: Hum Reprod. 2010 Jun;25(6):1383-97
references.pmid: 20378615
references.citation: Lab Anim. 1987 Jan;21(1):68-71
references.pmid: 3104669
references.citation: Cytogenet Genome Res. 2003;103(3-4):267-76
references.pmid: 15051947
references.citation: Mol Cell. 2000 Nov;6(5):989-98
references.pmid: 11106739
references.citation: Cell. 2010 Apr 16;141(2):331-43
references.pmid: 20403327
references.citation: Biol Reprod. 2012 Feb 29;86(2):42
references.pmid: 22088917
references.citation: Genes Dev. 2000 May 1;14(9):1085-97
references.pmid: 10809667
references.citation: Trends Genet. 2000 Sep;16(9):395-403
references.pmid: 10973068
references.citation: J Clin Endocrinol Metab. 1999 Oct;84(10):3443-50
references.pmid: 10522977
references.citation: J Neurochem. 2009 Jun;109(6):1570-83
references.pmid: 19383089
references.citation: Jikken Dobutsu. 1985 Apr;34(2):183-8
references.pmid: 4018151
references.citation: Reprod Toxicol. 2005 Jul-Aug;20(2):281-3
references.pmid: 15907664
references.citation: BMJ. 1994 Sep 3;309(6954):570-3
references.pmid: 8086942
references.citation: Science. 2000 Apr 14;288(5464):306-13
references.pmid: 10764638
references.citation: Mol Genet Metab. 2006 Sep-Oct;89(1-2):156-63
references.pmid: 16854607
references.citation: Genes Dev. 1997 Oct 15;11(20):2600-21
references.pmid: 9334324
references.citation: J Neurochem. 2000 Jun;74(6):2512-9
references.pmid: 10820213
references.citation: Endocr Rev. 2006 Jun;27(4):398-426
references.pmid: 16543383
references.citation: Cytogenet Genome Res. 2004;107(3-4):191-200
references.pmid: 15467364