Mutations in Serac1 or Synj2 cause proximal t haplotype-mediated male mouse sterility but not transmission ratio distortion.
Transmission ratio distortion (TRD) and sterility are male-specific quantitative trait phenomena associated with the mouse t haplotype. TRD occurs in t haplotype-heterozygous males and is caused by the deleterious action of distorter products on sperm bearing a wild-type responder locus. It has been proposed that t-mediated male sterility is a severe manifestation of TRD caused by homozygosity for distorter loci; thus, the distorter and sterility loci would be identical. In this, study a transgenic approach was used to identify the proximal sterility locus, tcs1 (S1), and test its role in TRD. Mice transgenic for a wild-type bacterial artificial chromosome (BAC) derived from the S1-critical region were bred onto t haplotype backgrounds. Mating results conclusively showed that the BAC is sufficient to restore fertility in otherwise sterile males. Multiple mutations were identified in the t alleles of Synj2 and Serac1, two genes in the BAC; thus, they are candidates for S1. In addition, whereas the BAC transgene rescued sterility, it had no effect on TRD. These results uncouple the proximal t haplotype sterility locus, S1, from TRD, demonstrating that S1 and the proximal distorter locus, D1, are not the same gene.
Schimenti
John C
JC
The Jackson Laboratory, Bar Harbor, ME 04609, USA.
Reynolds
Jennifer L
JL
Planchart
Antonio
A
D000818:Animals; D001483:Base Sequence; D022202:Chromosomes, Artificial, Bacterial; D004247:DNA; D006239:Haplotypes; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009419:Nerve Tissue Proteins; D004247:DNA; C097702:synaptojanin; D010744:Phosphoric Monoester Hydrolases
Biochem Biophys Res Commun. 1998 Jun 9;247(1):116-22
9636665
Genet Res. 1987 Feb;49(1):51-6
3569907
Nature. 1970 Aug 15;227(5259):680-5
5432063
Dev Biol. 2001 Dec 15;240(2):641-53
11784089
Genet Res. 1990 Oct-Dec;56(2-3):179-83
2272508
Mamm Genome. 2003 Dec;14(12):817-29
14724736
Genetics. 1976 Jun;83(2):361-72
17248720
Dev Biol. 1993 Jan;155(1):14-25
8416830
Nature. 1997 May 1;387(6628):101-5
9139830
Bioessays. 1999 Apr;21(4):304-12
10377892
Science. 1998 Sep 18;281(5384):1857-9
9743500
Cell. 1986 Jan 31;44(2):357-63
3943128
Genet Res. 1989 Dec;54(3):221-5
2620821
Dev Biol. 2001 May 1;233(1):204-13
11319869
Dev Biol. 2000 Jun 15;222(2):289-95
10837118
Nat Genet. 1997 Mar;15(3):285-8
9054943
Annu Rev Genet. 2003;37:393-408
14616067
Nature. 1999 Nov 11;402(6758):141-6
10647005
Blood. 1998 Apr 15;91(8):2753-9
9531585
Proc Natl Acad Sci U S A. 1989 May;86(9):3261-5
2717616
J Biol Chem. 1998 Jan 23;273(4):2306-11
9442075
Mamm Genome. 2001 Aug;12(8):668-70
11471064
Cell. 1984 Jun;37(2):621-8
6722884
J Biol Chem. 2002 Dec 20;277(51):49326-31
12379648
Curr Biol. 2003 Apr 15;13(8):659-63
12699622
Genetics. 1962 Mar;47:285-303
13888509
Genet Res. 1983 Oct;42(2):151-7
6667850
J Mol Biol. 1997 Apr 25;268(1):78-94
9149143
J Biol Chem. 1997 Dec 5;272(49):30817-21
9388224
J Biol Chem. 2001 Nov 2;276(44):41133-42
11498538
EMBO J. 1999 Jun 1;18(11):2991-3006
10357812
Genet Res. 1992 Feb;59(1):27-33
1572534
J Cell Biol. 1995 Aug;130(4):857-69
7642703
J Biol Chem. 2003 Jun 20;278(25):22574-7
12697762
Nature. 1989 Jan 26;337(6205):373-6
2911388
Biol Reprod. 2001 Nov;65(5):1606-15
11673282
Biol Reprod. 2002 May;66(5):1522-30
11967219
Genetics. 2000 Jun;155(2):803-12
10835401
Curr Biol. 2000 Nov 2;10(21):1383-6
11084340
Dev Biol. 1997 Nov 1;191(1):131-45
9356177
Genome Res. 2004 Feb;14(2):280-6
14762064
Cell. 1989 Sep 8;58(5):969-79
2570638
Biol Reprod. 1989 Feb;40(2):395-405
2720034
Genome Res. 2000 Nov;10(11):1772-87
11076862