A primer on the use of mouse models for identifying direct sex chromosome effects that cause sex differences in non-gonadal tissues

Biology of Sex Differences

Volumn 7, Issue 1, 2016, Pages 1-21

  Burgoyne, Paul S ^a   Arnold, Arthur P ^b  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Estradiol; Gonadal hormones; Sex chromosomes; Sex determination; Sexual differentiation; Testosterone; X chromosome; Y chromosome

Indexed keywords

EID: 85004098335     PISSN: None     EISSN: 20426410     Source Type: Journal    
DOI: 10.1186/s13293-016-0115-5     Document Type: Review

References (140)

1. Capel B, Lovell-Badge R. The Sry gene and sex determination in mammals. Adv Dev Biol. 1993;2:1-35.
2. Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Munsterberg A, Vivian N, Goodfellow P, Lovell-Badge R. A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature. 1990;346:245-50.
3. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R. Male development of chromosomally female mice transgenic for Sry. Nature. 1991;351:117-21.
4. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf A-M, Lovell-Badge R, Goodfellow PN. A gene from the human sex-determining region encoding a protein with homology to a conserved DNA binding motif. Nature. 1990;346:240-4.
5. Wilhelm D, Palmer S, Koopman P. Sex determination and gonadal development in mammals. Physiol Rev. 2007;87:1-28.
6. Arnold AP. Sex chromosomes and brain gender. Nat Rev Neurosci. 2004;5:701-8.
7. Burgoyne PS. A Y-chromosomal effect on blastocyst cell number in mice. Development. 1993;117:341-5.
8. Burgoyne PS, Thornhill AR, Kalmus Boudreau S, Darling SM, Bishop CE, Evans EP. The genetic basis of XX-XY differences present before sex differentiation in the mouse. Philosophical Trans Royal Soc London (Biology). 1995;350:253-61.
9. Corre C, Friedel M, Vousden DA, Metcalf A, Spring S, Qiu LR, Lerch JP, Palmert MR. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the four core genotype mouse model. Brain Struct Funct. 2014. doi:10.1007/s00429-014-0952-0.
10. Thornhill AR, Burgoyne PS. A paternally imprinted X chromosome retards the development of the early mouse embryo. Development. 1993;118:171-4.
11. Arnold AP, Reue K, Eghbali M, Vilain E, Chen X, Ghahramani N, Itoh Y, Li J, Link JC, Ngun T, Williams-Burris SM. The importance of having two X chromosomes. Philos Trans R Soc Lond B Biol Sci. 2016;371:20150113.
12. Arnold AP, Chen X. What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues? Front Neuroendocrinol. 2009;30:1-9.
13. Cox KH, Bonthuis PJ, Rissman EF. Mouse model systems to study sex chromosome genes and behavior: relevance to humans. Front Neuroendocrinol. 2014;35:405-19.
14. Charlesworth B, Charlesworth D. The degeneration of Y chromosomes. Philos Trans R Soc Lond B Biol Sci. 2000;355:1563-72.
15. Graves JA. Sex chromosome specialization and degeneration in mammals. Cell. 2006;124:901-14.
16. Burgoyne PS. The mammalian Y chromosome: a new perspective. Bioessays. 1998;20:363-6.
17. Graves JA. The origin and function of the mammalian Y chromosome and Y-borne gene - an evolving understanding. Bioessays. 1995;17:311-20.
18. Lahn BT, Page DC. Four evolutionary strata on the human X chromosome. Science. 1999;286:964-7.
19. Bellott DW, Hughes JF, Skaletsky H, Brown LG, Pyntikova T, Cho TJ, Koutseva N, Zaghlul S, Graves T, Rock S, et al. Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators. Nature. 2014;508:494-9.
20. Cortez D, Marin R, Toledo-Flores D, Froidevaux L, Liechti A, Waters PD, Grutzner F, Kaessmann H. Origins and functional evolution of Y chromosomes across mammals. Nature. 2014;508:488-93.
21. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature. 2003;423:825-37.
22. Soh YQ, Alfoldi J, Pyntikova T, Brown LG, Graves T, Minx PJ, Fulton RS, Kremitzki C, Koutseva N, Mueller JL, et al. Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes. Cell. 2014;159:800-13.
23. Cocquet J, Ellis PJ, Mahadevaiah SK, Affara NA, Vaiman D, Burgoyne PS. A genetic basis for a postmeiotic x versus y chromosome intragenomic conflict in the mouse. PLoS Genet. 2012;8:e1002900.
24. Burgoyne PS. Genetic homology and crossing over in the X and Y chromosomes of mammals. Hum Genet. 1982;61:85-90.
25. Burgoyne PS. Mammalian X and Y crossover. Nature. 1986;319:258-9.
26. Keitges EA, Rivest M, Siniscalco M, Gartler SM. X-linkage of steroid sulfatase in the mouse is evidence for a functional Y-linked allele. Nature. 1985;315:226-7.
27. Rouyer F, Simmler MC, Johnsson C, Vergnaud G, Cooke HJ, Weissenbach J. A gradient of sex linkage in the pseudoautosomal region of the human sex chromosomes. Nature. 1986;319:291-5.
28. Disteche CM. Dosage compensation of the sex chromosomes. Annu Rev Genet. 2012;46:537-60.
29. Itoh Y, Melamed E, Yang X, Kampf K, Wang S, Yehya N, Van Nas A, Replogle K, Band MR, Clayton DF, et al. Dosage compensation is less effective in birds than in mammals. J Biol. 2007;6:2.
30. Wu H, Luo J, Yu H, Rattner A, Mo A, Wang Y, Smallwood PM, Erlanger B, Wheelan SJ, Nathans J. Cellular resolution maps of X chromosome inactivation: implications for neural development, function, and disease. Neuron. 2014;81:103-19.
31. Migeon BR. The single active X in human cells: evolutionary tinkering personified. Hum Genet. 2011;130:281-93.
32. Deng X, Berletch JB, Nguyen DK, Disteche CM. X chromosome regulation: diverse patterns in development, tissues and disease. Nat Rev Genet. 2014;15:367-78.
33. Migeon BR. Females are mosaics: X inactivation and sex differences in disease. New York: Oxford University Press; 2007.
34. Itoh Y, Arnold AP. Are females more variable than males in gene expression? Meta-analysis of microarray datasets. Biol Sex Differ. 2015;6:18.
35. Lemos B, Araripe LO, Hartl DL. Polymorphic Y chromosomes harbor cryptic variation with manifold functional consequences. Science. 2008;319:91-3.
36. Lemos B, Branco AT, Hartl DL. Epigenetic effects of polymorphic Y chromosomes modulate chromatin components, immune response, and sexual conflict. Proc Natl Acad Sci U S A. 2010;107:15826-31.
37. Wijchers PJ, Festenstein RJ. Epigenetic regulation of autosomal gene expression by sex chromosomes. Trends Genet. 2011;27:132-40.
38. Wijchers PJ, Yandim C, Panousopoulou E, Ahmad M, Harker N, Saveliev A, Burgoyne PS, Festenstein R. Sexual dimorphism in mammalian autosomal gene regulation is determined not only by Sry but by sex chromosome complement as well. Dev Cell. 2010;19:477-84.
39. Morohashi K. The ontogenesis of the steroidogenic tissues. Genes Cells. 1997;2:95-106.
40. Parker KL, Rice DA, Lala DS, Ikeda Y, Luo X, Wong M, Bakke M, Zhao L, Frigeri C, Hanley NA, et al. Steroidogenic factor 1: an essential mediator of endocrine development. Recent Prog Horm Res. 2002;57:19-36.
41. Grgurevic N, Budefeld T, Rissman EF, Tobet SA, Majdic G. Aggressive behaviors in adult SF-1 knockout mice that are not exposed to gonadal steroids during development. Behav Neurosci. 2008;122:876-84.
42. Majdic G, Young M, Gomez-Sanchez E, Anderson P, Szczepaniak LS, Dobbins RL, McGarry JD, Parker KL. Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology. 2002;143:607-14.
43. Budefeld T, Grgurevic N, Tobet SA, Majdic G. Sex differences in brain developing in the presence or absence of gonads. Dev Neurobiol. 2008;68:981-95.
44. De Vries GJ, Rissman EF, Simerly RB, Yang L-Y, Scordalakes EM, Auger C, Swain A, Lovell-Badge R, Burgoyne PS, Arnold AP. A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits. J Neurosci. 2002;22:9005-14.
45. Arnold AP, Chen X, Link JC, Itoh Y, Reue K. Cell-autonomous sex determination outside of the gonad. Dev Dyn. 2013;242:371-9.
46. De Vries GJ. Minireview: sex differences in adult and developing brains: compensation, compensation, compensation. Endocrinology. 2004;145:1063-8.
47. Chen X, McClusky R, Chen J, Beaven SW, Tontonoz P, Arnold AP, Reue K. The number of x chromosomes causes sex differences in adiposity in mice. PLoS Genet. 2012;8:e1002709.
48. Li J, Chen X, McClusky R, Ruiz-Sundstrom M, Itoh Y, Umar S, Arnold AP, Eghbali M. The number of X chromosomes influences protection from cardiac ischaemia/reperfusion injury in mice: one X is better than two. Cardiovasc Res. 2014;102:375-84.
49. Smith-Bouvier DL, Divekar AA, Sasidhar M, Du S, Tiwari-Woodruff SK, King JK, Arnold AP, Singh RR, Voskuhl RR. A role for sex chromosome complement in the female bias in autoimmune disease. J Exp Med. 2008;205:1099-108.
50. Chen X, McClusky R, Itoh Y, Reue K, Arnold AP. X and Y chromosome complement influence adiposity and metabolism in mice. Endocrinology. 2013;154:1092-104.
51. Itoh Y, Mackie R, Kampf K, Domadia S, Brown JD, O'Neill R, Arnold AP. Four core genotypes mouse model: localization of the Sry transgene and bioassay for testicular hormone levels. BMC Res Notes. 2015;8:69.
52. Manwani B, Bentivegna K, Benashski SE, Venna VR, Xu Y, Arnold AP, McCullough LD. Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement. J Cereb Blood Flow Metab. 2015;35:221-9.
53. Du S, Itoh N, Askarinam S, Hill H, Arnold AP, Voskuhl RR. XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2014;111:2806-11.
54. Mahadevaiah SK, Lovell-Badge R, Burgoyne PS. Tdy-negative XY, XXY and XYY female mice: breeding data and synaptonemal complex analysis. J Reprod Fertil. 1993;97:151-60.
55. Vernet N, Szot M, Mahadevaiah SK, Ellis PJ, Decarpentrie F, Ojarikre OA, Rattigan A, Taketo T, Burgoyne PS. The expression of Y-linked Zfy2 in XY mouse oocytes leads to frequent meiosis 2 defects, a high incidence of subsequent early cleavage stage arrest and infertility. Development. 2014;141:855-66.
56. Kopsida E, Lynn PM, Humby T, Wilkinson LS, Davies W. Dissociable effects of Sry and sex chromosome complement on activity, feeding and anxiety-related behaviours in mice. PLoS One. 2013;8:e73699.
57. Burgoyne PS. Genetics of XX and XO sex reversal in the mouse. In: Wachtel S, editor. Evolutionary mechanisms of sex determination. Boca Raton, Florida: CRC Press Inc; 1988. p. 161-9.
58. Hunt PA, Worthman C, Levinson H, Stallings J, LeMaire R, Mroz K, Park C, Handel MA. Germ cell loss in the XXY male mouse: altered X chromosome dosage affects prenatal development. Mol Reprod Dev. 1998;49:101-11.
59. Gatewood JD, Wills A, Shetty S, Xu J, Arnold AP, Burgoyne PS, Rissman EF. Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice. J Neurosci. 2006;26:2335-42.
60. Holaskova I, Franko J, Goodman RL, Arnold AP, Schafer R. The XX sex chromosome complement is required in male and female mice for enhancement of immunity induced by exposure to 3,4-dichloropropionanilide. Am J Reprod Immunol. 2015;74:136-47.
61. Wagner CK, Xu J, Pfau JL, Quadros PS, De Vries GJ, Arnold AP. Neonatal mice possessing an Sry transgene show a masculinized pattern of progesterone receptor expression in the brain independent of sex chromosome status. Endocrinology. 2004;145:1046-9.
62. McPhie-Lalmansingh AA, Tejada LD, Weaver JL, Rissman EF. Sex chromosome complement affects social interactions in mice. Horm Behav. 2008;54:565-70.
63. McCullough LD, Mirza MA, Xu Y, Bentivegna K, Steffens EB, Ritzel R, Liu F: Stroke sensitivity in the aged: sex chromosome complement vs. gonadal hormones. Aging (Albany NY). 2016. Doi: 10.18632/aging.100997.
64. Palaszynski KM, Smith DL, Kamrava S, Burgoyne PS, Arnold AP, Voskuhl RR. A yin-yang effect between sex chromosome complement and sex hormones on the immune response. Endocrinology. 2005;146:3280-5.
65. Sasidhar MV, Itoh N, Gold SM, Lawson GW, Voskuhl RR. The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY. Ann Rheum Dis. 2012;71:1418-22.
66. Arnold AP. The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of all mammalian tissues. Horm Behav. 2009;55:570-8.
67. Chen X, Grisham W, Arnold AP. X chromosome number causes sex differences in gene expression in adult mouse striatum. Eur J Neurosci. 2009;29:768-76.
68. Gioiosa L, Chen X, Watkins R, Umeda EA, Arnold AP. Sex chromosome complement affects nociception and analgesia in newborn mice. J Pain. 2008;9:962-9.
69. Becker JB, Arnold AP, Berkley KJ, Blaustein JD, Eckel LA, Hampson E, Herman JP, Marts S, Sadee W, Steiner M, et al. Strategies and methods for research on sex differences in brain and behavior. Endocrinology. 2005;146:1650-73.
70. Eicher EM, Hale DW, Hunt PA, Lee BK, Tucker PK, King TR, Eppig JT, Washburn LL. The mouse Y* chromosome involves a complex rearrangement, including interstitial positioning of the pseudoautosomal region. Cytogenet Cell Genet. 1991;57:221-30.
71. Burgoyne PS, Mahadevaiah SK, Perry J, Palmer SJ, Ashworth A. The Y* rearrangement in mice: new insights into a perplexing PAR. Cytogenet Cell Genet. 1998;80:37-40.
72. Wolstenholme JT, Rissman EF, Bekiranov S. Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes. Genes Brain Behav. 2013;12:166-80.
73. Vernet N, Mahadevaiah SK, Yamauchi Y, Decarpentrie F, Mitchell MJ, Ward MA, Burgoyne PS. Mouse Y-linked Zfy1 and Zfy2 are expressed during the male-specific interphase between meiosis I and meiosis II and promote the 2nd meiotic division. PLoS Genet. 2014;10:e1004444.
74. Yamauchi Y, Riel JM, Ruthig V, Ward MA. Mouse Y-encoded transcription factor Zfy2 is essential for sperm formation and function in assisted fertilization. PLoS Genet. 2015;11:e1005476.
75. Hunt PA. Survival of XO mouse fetuses: effect of parental origin of the X chromosome or uterine environment? Development. 1991;111:1137-41.
76. Lue YH, Wang C, Liu PY, Erkilla K, Swerdloff RS. Insights into the pathogenesis of XXY phenotype from comparison of the clinical syndrome with an experimental XXY mouse model. Pediatr Endocrinol Rev. 2010;8 Suppl 1:140-4.
77. Burgoyne PS, Biggers JD. The consequences of X-dosage deficiency in the germ line: impaired development in vitro of preimplantation embryos from XO mice. Dev Biol. 1976;51:109-17.
78. Burgoyne PS, Tam PPL, Evans EP. Retarded development of XO conceptuses during early pregnancy in the mouse. J Reprod Fertil. 1983;68:387-93.
79. Jamieson RV, Tan S-S, Tam PPL. Retarded postimplantation development of X0 mouse embryos: impact of the parental origin of the monosomic X chromosome. Dev Biol. 1998;201:13-25.
80. Bonthuis PJ, Huang WC, Stacher Horndli CN, Ferris E, Cheng T, Gregg C. Noncanonical genomic imprinting effects in offspring. Cell Rep. 2015;12:979-91.
81. Lee JT, Bartolomei MS. X-inactivation, imprinting, and long noncoding RNAs in health and disease. Cell. 2013;152:1308-23.
82. Mak W, Nesterova TB, de Napoles M, Appanah R, Yamanaka S, Otte AP, Brockdorff N. Reactivation of the paternal X chromosome in early mouse embryos. Science. 2004;303:666-9.
83. Okamoto I, Otte AP, Allis CD, Reinberg D, Heard E. Epigenetic dynamics of imprinted X inactivation during early mouse development. Science. 2004;303:644-9.
84. Banzai M, Omoe K, Ishikawa H, Endo A. Viability, development and incidence of chromosome anomalies of preimplantation embryos from XO mice. Cytogen Cell Genet. 1995;70:273-7.
85. Davies W, Isles A, Smith R, Karunadasa D, Burrmann D, Humby T, Ojarikre O, Biggin C, Skuse D, Burgoyne P, Wilkinson L. Xlr3b is a new imprinted candidate for X-linked parent-of-origin effects on cognitive function in mice. Nat Genet. 2005;37:625-9.
86. Raefski AS, O'Neill MJ. Identification of a cluster of X-linked imprinted genes in mice. Nat Genet. 2005;37:620-4.
87. Babak T, DeVeale B, Tsang EK, Zhou Y, Li X, Smith KS, Kukurba KR, Zhang R, Li JB, van der Kooy D, et al. Genetic conflict reflected in tissue-specific maps of genomic imprinting in human and mouse. Nat Genet. 2015;47:544-9.
88. Hook EB, Warburton D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45, X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss. Hum Genet. 2014;133:417-24.
89. Berletch JB, Ma W, Yang F, Shendure J, Noble WS, Disteche CM, Deng X. Escape from X inactivation varies in mouse tissues. PLoS Genet. 2015;11:e1005079.
90. Ellis PJ, Bacon J, Affara NA. Association of Sly with sex-linked gene amplification during mouse evolution: a side effect of genomic conflict in spermatids? Hum Mol Genet. 2011;20:3010-21.
91. Yang F, Babak T, Shendure J, Disteche CM. Global survey of escape from X inactivation by RNA-sequencing in mouse. Genome Res. 2010;20:614-22.
92. Bonthuis PJ, Rissman EF. Neural growth hormone implicated in body weight sex differences. Endocrinology. 2013;154:3826-35.
93. Lopes AM, Burgoyne PS, Ojarikre A, Bauer J, Sargent CA, Amorim A, Affara NA. Transcriptional changes in response to X chromosome dosage in the mouse: implications for X inactivation and the molecular basis of Turner Syndrome. BMC Genomics. 2010;11:82.
94. Xu J, Deng X, Disteche CM. Sex-specific expression of the X-linked histone demethylase gene Jarid1c in brain. PLoS One. 2008;3:e2553.
95. Xu J, Deng X, Watkins R, Disteche CM. Sex-specific differences in expression of histone demethylases Utx and Uty in mouse brain and neurons. J Neurosci. 2008;28:4521-7.
96. Xu J, Taya S, Kaibuchi K, Arnold AP. Sexually dimorphic expression of Usp9x is related to sex chromosome complement in adult mouse brain. Eur J Neurosci. 2005;21:3017-22.
97. Xu J, Watkins R, Arnold AP. Sexually dimorphic expression of the X-linked gene Eif2s3x mRNA but not protein in mouse brain. Gene Expr Patterns. 2006;6:146-55.
98. Wang H, Hu YC, Markoulaki S, Welstead GG, Cheng AW, Shivalila CS, Pyntikova T, Dadon DB, Voytas DF, Bogdanove AJ, et al. TALEN-mediated editing of the mouse Y chromosome. Nat Biotechnol. 2013;31:530-2.
99. Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F, Jaenisch R. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell. 2013;153:910-8.
100. Matsubara Y, Kato T, Kashimada K, Tanaka H, Zhi Z, Ichinose S, Mizutani S, Morio T, Chiba T, Ito Y, et al. TALEN-mediated gene disruption on Y chromosome reveals critical role of EIF2S3Y in mouse spermatogenesis. Stem Cells Dev. 2015;24:1164-70.
101. Singh P, Schimenti JC, Bolcun-Filas E. A mouse geneticist's practical guide to CRISPR applications. Genetics. 2015;199:1-15.
102. Mazeyrat S, Saut N, Grigoriev V, Mahadevaiah SK, Ojarikre OA, Rattigan A, Bishop C, Eicher EM, Mitchell MJ, Burgoyne PS. A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis. Nat Genet. 2001;29:49-53.
103. Cocquet J, Ellis PJ, Yamauchi Y, Mahadevaiah SK, Affara NA, Ward MA, Burgoyne PS. The multicopy gene Sly represses the sex chromosomes in the male mouse germline after meiosis. PLoS Biol. 2009;7:e1000244.
104. Vernet N, Mahadevaiah SK, Decarpentrie F, Longepied G, de Rooij DG, Burgoyne PS, Mitchell MJ. Mouse Y-encoded transcription factor Zfy2 is essential for sperm head remodelling and sperm tail development. PLoS One. 2016;11:e0145398.
105. Shpargel KB, Sengoku T, Yokoyama S, Magnuson T. UTX and UTY demonstrate histone demethylase-independent function in mouse embryonic development. PLoS Genet. 2012;8:e1002964.
106. Arnold AP. Conceptual frameworks and mouse models for studying sex differences in physiology and disease: why compensation changes the game. Exp Neurol. 2014;259:2-9.
107. Chen X, Wang L, Loh DH, Colwell CS, Tache Y, Reue K, Arnold AP. Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes. Horm Behav. 2015;75:55-63.
108. Royo H, Polikiewicz G, Mahadevaiah SK, Prosser H, Mitchell M, Bradley A, de Rooij DG, Burgoyne PS, Turner JM. Evidence that meiotic sex chromosome inactivation is essential for male fertility. Curr Biol. 2010;20:2117-23.
109. Vernet N, Mahadevaiah SK, Ojarikre OA, Longepied G, Prosser HM, Bradley A, Mitchell MJ, Burgoyne PS. The Y-encoded gene Zfy2 acts to remove cells with unpaired chromosomes at the first meiotic metaphase in male mice. Curr Biol. 2011;21:787-93.
110. Wright WE, Sassoon DA, Lin VK. Myogenin, a factor regulating myogenesis, has a domain homologous to MyoD. Cell. 1989;56:607-17.
111. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402-8.
112. Burgoyne PS, Evans EP. A high frequency of XO offspring from X(Paf)Y* male mice: evidence that the Paf mutation involves an inversion spanning the X PAR boundary. Cytogenet Cell Genet. 2000;91:57-61.
113. Lane PW, Davisson MT. Patchy fur (Paf), a semidominant X-linked gene associated with a high level of X-Y nondisjunction in male mice. J Hered. 1990;81:43-50.
114. Koehler KE, Millie EA, Cherry JP, Burgoyne PS, Evans EP, Hunt PA, Hassold TJ. Sex-specific differences in meiotic chromosome segregation revealed by dicentric bridge resolution in mice. Genetics. 2002;162:1367-79.
115. Ishikawa H, Rattigan A, Fundele R, Burgoyne PS. Effects of sex chromosome dosage on placental size in mice. Biol Reprod. 2003;69:483-8.
116. Mahadevaiah SK, Odorisio T, Elliott DJ, Rattigan A, Szot M, Laval SH, Washburn LL, McCarrey JR, Cattanach BM, Lovell-Badge R, Burgoyne PS. Mouse homologues of the human AZF candidate gene RBM are expressed in spermatogonia and spermatids, and map to a Y chromosome deletion interval associated with a high incidence of sperm abnormalities. Hum Mol Genet. 1998;7:715-27.
117. Capel B, Rasberry C, Dyson J, Bishop CE, Simpson E, Vivian N, Lovell-Badge R, Rastan S, Cattanach BM. Deletion of Y chromosome sequences located outside the testis determining region can cause XY female sex reversal. Nat Genet. 1993;5:301-7.
118. Laval SH, Reed V, Blair HJ, Boyd Y. The structure of DXF34, a human X-linked sequence family with homology to a transcribed mouse Y-linked repeat. Mamm Genome. 1997;8:689-91.
119. Rodriguez TA, Burgoyne PS. Spermatogenic failure in male mice with four sex chromosomes. Chromosoma. 2001;110:124-9.
120. Touré A, Grigoriev V, Mahadevaiah SK, Rattigan A, Ojarikre OA, Burgoyne PS. A protein encoded by a member of the multicopy Ssty gene family located on the long arm of the mouse Y chromosome is expressed during sperm development. Genomics. 2004;83:140-7.
121. Chen X, Watkins R, Delot E, Reliene R, Schiestl RH, Burgoyne PS, Arnold AP. Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes. Dev Neurobiol. 2008;68:265-73.
122. Palmer S, Perry J, Kipling D, Ashworth A. A gene spans the pseudoautosomal boundary in mice. Proc Natl Acad Sci U S A. 1997;94:12030-5.
123. Kipling D, Salido EC, Shapiro LJ, Cooke HJ. High frequency de novo alterations in the long-range genomic structure of the mouse pseudoautosomal region. Nat Genet. 1996;13:78-82.
124. Salido EC, Li XM, Yen PH, Martin N, Mohandas TK, Shapiro L. Cloning and expression of the mouse pseudoautosomal steroid sulphatase gene (Sts). Nat Genet. 1996;13:83-6.
125. Trent S, Fry JP, Ojarikre OA, Davies W. Altered brain gene expression but not steroid biochemistry in a genetic mouse model of neurodevelopmental disorder. Mol Autism. 2014;5:21.
126. Trent S, Dean R, Veit B, Cassano T, Bedse G, Ojarikre OA, Humby T, Davies W. Biological mechanisms associated with increased perseveration and hyperactivity in a genetic mouse model of neurodevelopmental disorder. Psychoneuroendocrinology. 2013;38:1370-80.
127. Hughes JF, Skaletsky H, Koutseva N, Pyntikova T, Page DC. Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals. Genome Biol. 2015;16:104.
128. Elliott DJ, Ma K, Kerr SM, Thakrar R, Speed R, Chandley AC, Cooke H. An RBM homologue maps to the mouse Y chromosome and is expressed in germ cells. Hum Mol Genet. 1996;5:869-74.
129. Dreumont N, Bourgeois CF, Lejeune F, Liu Y, Ehrmann IE, Elliott DJ, Stevenin J. Human RBMY regulates germline-specific splicing events by modulating the function of the serine/arginine-rich proteins 9G8 and Tra2-{beta}. J Cell Sci. 2010;123:40-50.
130. Kay GF, Ashworth A, Penny GD, Dunlop M, Swift S, Brockdorff N, Rastan S. A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1. Nature. 1991;354:486-9.
131. Mitchell MJ, Woods DR, Tucker PK, Opp JS, Bishop CE. Homology of a candidate spermatogenic gene from the mouse Y chromosome to the ubiquitin-activating enzyme E1. Nature. 1991;354:483-6.
132. Akimoto C, Kitagawa H, Matsumoto T, Kato S. Spermatogenesis-specific association of SMCY and MSH5. Genes Cells. 2008;13:623-33.
133. Agulnik AI, Mitchell MJ, Lerner JL, Woods DR, Bishop CE. A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens. Hum Mol Gen. 1994;3:873-8.
134. Decarpentrie F, Vernet N, Mahadevaiah SK, Longepied G, Streichemberger E, Aknin-Seifer I, Ojarikre OA, Burgoyne PS, Metzler-Guillemain C, Mitchell MJ. Human and mouse ZFY genes produce a conserved testis-specific transcript encoding a zinc finger protein with a short acidic domain and modified transactivation potential. Hum Mol Genet. 2012;21:2631-45.
135. Greenfield A, Scott D, Pennisi D, Ehrmann I, Ellis P, Cooper L, Simpson E, Koopman P. An H-YDb epitope is encoded by a novel mouse Y chromosome gene. Nat Genet. 1996;14:474-8.
136. Brown GM, Furlong RA, Sargent CA, Erickson RP, Longepied G, Mitchell M, Jones MH, Hargreave TB, Cooke HJ, Affara NA. Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene. Hum Mol Gen. 1998;7:97-108.
137. Sun C, Skaletsky H, Birren B, Devon K, Tang Z, Silber S, Oates R, Page D. An Azoospermic man with a de novo point mutation in the Y-chromosomal gene USP9Y. Nat Genet. 1999;23:429-32.
138. Mazeyrat S, Saut N, Sargent CA, Grimmond S, Longepied G, Ehrmann IE, Ellis PS, Greenfield A, Affara NA, Mitchell MJ. The mouse Y chromosome interval necessary for spermatogonial proliferation is gene dense with syntenic homology to the human AZFa region. Hum Mol Genet. 1998;7:1713-24.
139. Ehrmann IE, Ellis PS, Mazeyrat S, Duthie S, Brockdorff N, Mattei MG, Gavin MA, Affara NA, Brown GM, Simpson E, et al. Characterization of genes encoding translation initiation factor eIF-2gamma in mouse and human: sex chromosome localisation, escape from X-inactivation and evolution. Hum Mol Gen. 1998;7:1725-37.
140. Xu J, Burgoyne PS, Arnold AP. Sex differences in sex chromosome gene expression in mouse brain. Hum Mol Genet. 2002;11:1409-19.