Deletion of Otx2 in GnRH neurons results in a mouse model of hypogonadotropic hypogonadism

Molecular Endocrinology

Volumn 25, Issue 5, 2011, Pages 833-846

  Diaczok, Daniel ^a   Divall, Sara ^a   Matsuo, Isao ^b   Wondisford, Fredric E ^a   Wolfe, Andrew M ^a   Radovick, Sally ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b RESEARCH INSTITUTE FOR MATERNAL AND CHILD HEALTH   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 3; FOLLITROPIN BETA SUBUNIT; GONADORELIN; LUTEINIZING HORMONE BETA SUBUNIT; MESSENGER RNA; SEX HORMONE; TRANSCRIPTION FACTOR OTX2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BRAIN NERVE CELL; CONTROLLED STUDY; CORPUS LUTEUM; ESTRUS CYCLE; FEMALE; FOLLITROPIN BLOOD LEVEL; GENE DELETION; HYPOGONADOTROPIC HYPOGONADISM; HYPOTHALAMUS; INFERTILITY; KNOCKOUT MOUSE; LEYDIG CELL; LUTEINIZING HORMONE BLOOD LEVEL; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PUBERTY; SERTOLI CELL;

ANIMALS; APOPTOSIS; CASPASE 3; CORPUS LUTEUM; ESTRUS; FEMALE; GENE DELETION; GENETIC ENGINEERING; GONADOTROPIN-RELEASING HORMONE; HYPOGONADISM; HYPOTHALAMUS; INFERTILITY, FEMALE; LUTEINIZING HORMONE, BETA SUBUNIT; MALE; MICE; MICE, KNOCKOUT; NEURONS; OTX TRANSCRIPTION FACTORS; PROSENCEPHALON; SEXUAL MATURATION; TESTIS;

MAMMALIA;

EID: 79955758792     PISSN: 08888809     EISSN: None     Source Type: Journal    
DOI: 10.1210/me.2010-0271     Document Type: Article

References (67)

1. Gamble JA, Karunadasa DK, Pape JR, Skynner MJ, Todman MG, Bicknell RJ, Allen JP, Herbison AE 2005 Disruption of ephrin signaling associates with disordered axophilic migration of the gonadotropin-releasing hormone neurons. J Neurosci 25:3142-3150
2. Schwanzel-Fukuda M, Bick D, Pfaff DW 1989 Luteinizing hormonereleasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Brain Res Mol Brain Res 6:311-326
3. Cattanach BM, Iddon CA, Charlton HM, Chippa SA, Fink G 1977 Gonadotropin-releasing hormone deficiency in a mutant mouse with hypogonadism. Nature 269:338-340
4. Mason AJ, Hayflick JS, Zoeller RT, Young 3rd WS, Phillips HS, Nikolics K, Seeburg PH 1986 A deletion truncating the gonadotropin-releasing hormone gene is responsible for hypogonadism in the hpg mouse. Science 234:1366-1371
5. Chan YM, de Guillebon A, Lang-Muritano M, Plummer L, Cerrato F, Tsiaras S, Gaspert A, Lavoie HB, Wu CH, Crowley Jr WF, Amory JK, Pitteloud N, Seminara SB 2009 GNRH1 mutations in patients with idiopathic hypogonadotropic hypogonadism. Proc Natl Acad Sci USA 106:11703-11708
6. Trarbach EB, Silveira LG, Latronico AC 2007 Genetic insights into human isolated gonadotropin deficiency. Pituitary 10:381-391
7. Seminara SB, Hayes FJ, Crowley Jr WF 1998 Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann's syndrome): pathophysiological and genetic considerations. Endocr Rev 19:521-539
8. Bhangoo A, Jacobson-Dickman E 2009 The genetics of idiopathic hypogonadotropic hypogonadism: unraveling the biology of human sexual development. Pediatr Endocrinol Rev 6:395-404
9. Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P, Lombès M, Millar RP, Guiochon-Mantel A, Young J 2009 Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. N Engl J Med 360:2742-2748
10. Miller NL, Wevrick R, Mellon PL 2009 Necdin, a Prader-Willi syndrome candidate gene, regulates goandotropin-releasing hormone neurons during development. Hum Mol Genet 18:248-260
11. Bianco S, Kaiser U 2009 The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol 5:569-576
12. Diaczok D, Romero C, Zunich J, Marshall I, Radovick S 2008 A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency. J Clin Endocrinol Metab 93: 4351-4359
13. Dateki S, Fukami M, Sato N, Muroya K, Adachi M, Ogata T 2008 OTX2 mutation in a patient with anophthalmia, short stature, and partial growth hormone deficiency: functional studies using the IRBP, HESX1, and POU1F1 promoters. J Clin Endocrinol Metab 93:3697-3702
14. Dateki S, Kosaka K, Hasegawa K, Tanaka H, Azuma N, Yokoya S, Muroya K, Adachi M, Tajima T, Motomura K, Kinoshita E, Moriuchi H, Sato N, Fukami M, Ogata T 2010 Heterozygous orthodenticle homeobox 2 mutations are associated with variable pituitary phenotype. J Clin Endocrinol Metab 95:756-764
15. Schwanzel-Fukuda M, Pfaff DW 1989 Origin of luteinizing hormone- releasing hormone neurons. Nature 338:161-164
16. Wray S, Grant P, Gainer H 1989 Evidence that cells expressing luteinizing hormone-releasing hormone mRNA in the mouse are derived from progenitor cells in the olfactory placode. Proc Natl Acad Sci USA 86:8132-8136
17. Kramer PR, Guerrero G, Krishnamurthy R, Mitchell PJ, Wray S 2000 Ectopic expression of luteinizing hormone-releasing hormone and peripherin in the respiratory epithelium of mice lacking transcription factor AP-2α. Mech Dev 94:79-94
18. Gill JC, Moenter SM, Tsai PS 2004 Developmental regulation of gonadotropin-releasing hormone neurons by fibroblast growth factor signaling. Endocrinology 145:3830-3839
19. Kramer PR, Wray S 2000 Novel gene expressed in nasal region influences outgrowth of olfactory axons and migration of luteinizing hormone-releasing hormone (LHRH) neurons. Genes Dev 14: 1824-1834
20. Tobet SA, Chickering TW, King JC, Stopa EG, Kim K, Kuo-Leblank V, Schwarting GA 1996 Expression of gamma-aminobutyric acid and gonadotropin-releasing hormone during neuronal migration through the olfactory system. Endocrinology 137:5415-5420
21. Fueshko SM, Key S, Wray S 1998 GABA inhibits migration of luteinizing hormone-releasing hormone neurons in embryonic olfactory explants. J Neurosci 18:2560-2569
22. Schwarting GA, Kostek C, Bless EP, Ahmad N, Tobet SA 2001 Deleted in colorectal cancer (DCC) regulates the migration of luteinizing hormone-releasing hormone neurons to the basal forebrain. J Neurosci 21:911-919
23. Tobet SA, Schwarting GA 2006 Minireview: recent progress in gonadotroprin-releasing hormone neuronal migration. Endocrinology 147:1159-1165
24. Pierce A, Bliesner B, Xu M, Nielsen-Preiss S, Lemke G, Tobet S, Wierman ME 2008 Axl and Tyro3 modulate female reproduction by influencing gonadotropin-releasing hormone neuron survival and migration. Mol Endocrinol 22:2481-2495
25. Wu TJ, Gibson MJ, Rogers MC, Silverman AJ 1997 New observations on the development of the gonadotropin-releasing hormone system in the mouse. J Neurobiol 33:938-998
26. Kinder SJ, Tsang TE, Ang SL, Behringer RR, Tam PP 2001 Defects of the body plan of mutant embryos lacking Lim1, Otx2, or Hnf3β activity. Int J Dev Biol 45:347-355
27. Rhinn M, Dierich A, Shawlot W, Behringer RR, Le Meur M, Ang SL 1998 Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification. Development 125:845-856
28. Ang SL, Jin O, Rhinn M, Daigle N, Stevenson L, Rossant J 1996 A targeted mouse Otx2 mutation leads to severe defects in gastrulation and formation of axial mesoderm and to deletion of rostral brain. Development 122:243-252
29. Vernay B, Koch M, Vaccarino F, Briscoe J, Simeone A, Kageyama R, Ang SL 2005 Otx2 regulates subtype specification and neurogenesis in the midbrain. J Neurosci 25:4856-4867
30. Brodski C, Weisenhorn DM, Signore M, Sillaber I, Oesterheld M, Broccoli V, Acampora D, Simeone A, Wurst W 2003 Location and size of dopaminergic and serotonergic cell populations are controlled by the position of the midbrain-hindbrain organizer. J Neurosci 23:4199-4207
31. Fossat N, Chatelain G, Brun G, Lamonerie T 2006 Temporal and spatial delineation of mouse Otx2 functions by conditional selfknockout. EMBO Rep 7:824-830
32. Omodei D, Acampora D, Mancuso P, Prakash N, Di Giovannantonio LG, Wurst W, Simeone A 2008 Anterior-posterior graded response to Otx2 controls proliferation and differentiation of dopaminergic progenitros in the ventral mesencephalon. Development 135:3459-3470
33. Puelles E, Acampora D, Lacroix E, Signore M, Annino A, Tuorto F, Filosa S, Corte G, Wurst W, Ang SL, Simeone A 2003 Otx dosedependent integrated control of antero-posterior and dorso-ventral patterning of midbrain. Nat Neurosci 6:453-460
34. Puelles E, Annino A, Tuorto F, Usiello A, Acampora D, Czerny T, Brodski C, Ang SL, Wurst W, Simeone A 2004 Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain. Development 131:2037-2048
35. Hide T, Hatakeyama J, Kimura-Yoshida C, Tian E, Takeda N, Ushio Y, Shiroishi T, Aizawa S, Matsuo I 2002 Genetic modifiers of otocephalic phenotypes in Otx2 heterozygous mutant mice. Development 129:4347-4357
36. Wyatt A, Bakrania P, Bunyan DJ, Osborne RJ, Crolla JA, Salt A, Ayuso C, Newbury-Ecob R, Abou-Rayyah Y, Collin JR, Robinson D, Ragge N 2008 Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma. Hum Mutat 29:E278-E283
37. Tajima T, Ohtake A, Hoshino M, Amemiya S, Sasaki N, Ishizu K, Fujieda K 2009 OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary. J Clin Endocrinol Metab 94: 314-319
38. Simeone A, Acampora D, Mallamaci A, Stornaiuolo A, D'Apice MR, Nigro V, Boncinelli E 1993 A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. EMBO J 12:2735-2747
39. Inverardi F, Beolchi MS, Ortino B, Moroni RF, Regondi MC, Amadeo A, Frassoni C 2007 GABA immunoreactivity in the developing rat thalamus and Otx2 homeoprotein expression in migrating neurons. Brain Res Bull 73:64-74
40. Rebsam A, Mason CA 2008 Otx2's incredible journey. Cell 134: 386-387
41. Sugiyama S, Di Nardo AA, Aizawa S, Matsuo I, Volovitch M, Prochiantz A, Hensch TK 2008 Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell 134:508-520
42. Rath MF, Muñoz E, Ganguly S, Morin F, Shi Q, Klein DC, Moller M 2006 Expression of the Otx2 homeobox gene in the developingmammalian brain; embryonic and adult expression in the pineal gland. J Neurochem 97:556-566
43. Acampora D, Mazan S, Lallemand Y, Avantaggiato V, Maury M, Simeone A, Brûlet P 1995 Forebrain and midbrain regions are deleted in Otx2-/- mutants due to a defective anterior neuroectoderm specification during gastrulation. Development 121:3279-3290
44. Matsuo I, Kuratani S, Kimura C, Takeda N, Aizawa S 1995 Mouse Otx2 functions in the formation and patterning of rostral head. Genes Dev 9:2646-2658
45. Kim HH, Wolfe A, Cohen RN, Eames SC, Johnson AL, Wieland CN, Radovick S 2007 In vivo identification of a 107-base pair promoter element mediating neuron-specific expression of mouse gonadotropin-releasing hormone. Mol Endocrinol 21:457-471
46. Kelley CG, Lavorgna G, Clark ME, Boncinelli E, Mellon PL 2000 The Otx2 homeoprotein regulates expression from the gonadotropin-releasing hormone proximal promoter. Mol Endocrinol 14: 1246-1256
47. Larder R, Mellon PL 2009 Otx2 induction of the gonadotropinreleasing hormone promoter is modulated by direct interaction with Grg co-repressors. J Biol Chem 284:16966-16978
48. Tian E, Kimura C, Takeda N, Aizawa S, Matsuo I 2002 Otx2 is required to respond to signals from anterior neural ridge for forebrain specification. Dev Biol 242:204-223
49. Wolfe A, Divall S, Singh SP, Nikrodhanond AA, Baria AT, Le WW, Hoffman GE, Radovick S 2008 Temporal and spatial regulation of CRE recombinase expression in GnRH neurons in the mouse. J Neuroendocrinol 20:909-916
50. Franklin KBJ, Paxinos G 1997 The mouse brain in stereotaxic coordinates. San Diego: Academic Press
51. Silverman AJ, Livne I, Witkin JW 1994 The gonadotropin-releasing hormone (GnRH), neuronal systems: immunocytochemistry and in situ hybridization. In: Knobil E, Neill JD, eds. The physiology of reproduction. New York: Raven Press; 1683-1709
52. King JC, Tobet SA, Snavely FL, Arimura AA 1982 LHRH immunopositive cells and their projections to the median eminence and organum vasculosum of the lamina terminalis. J Comp Neurol 209: 287-300
53. Witkin JW, Paden CM, Silverman AJ 1982 The luteinizing hormone- releasing hormone (LHRH) systems in the rat brain. Neuroendocrinology 35:429-438
54. Gallo RV 1981 Pulsatile LH release during the ovulatory LH surge on proestrus in the rat. Biol Reprod 24:100-104
55. Gill JC, Wadas B, Chen P, Portillo W, Reyna A, Jorgensen E, Mani S, Schwarting GA, Moenter SM, Tobet S, Kaiser UB 2008 The gonadotropin-releasing hormone (GnRH) neuronal population is normal in size and distribution in GnRH-deficient and GnRH receptor-mutant hypogonadal mice. Endocrinology 149:4596-4604
56. Lapatto R, Pallais JC, Zhang D, Chan YM, Mahan A, Cerrato F, Le WW, Hoffman GE, Seminara SB 2007 Kiss1-/- mice exhibit more variable hypogonadism than Gpr54-/- mice. Endocrinology 148: 4927-4936
57. Herbison AE, Porteous R, Pape JR, Mora JM, Hurst PR 2008 Gonadotropin-releasing hormone neuron requirements for puberty, ovulation, and fertility. Endocrinology 149:597-604
58. McNeilly AS, Crawford JL, Taragnat C, Nicol L, McNeilly JR 2003 The differential secretion of FSH and LH: regulation through genes, feedback and packaging. Reprod Suppl 61:463-476
59. Gibson MJ, Kasowski H, Dobrjansky A 1994 Continuous gonadotropin- releasing hormone infusion stimulates dramatic gonadal development in hypogonadal female mice. Biol Reprod 50:680-685
60. Wide L, Eriksson K, Sluss PM, Hall JE 2009 Serum half-life of pituitary gonadotropins is decreased by sulfonation and increased by sialylation in women. J Clin Endocrinol Metab 94:958-964
61. Brown-Grant K, Davidson JM, Greig F 1973 Induced ovulation in albino rats exposed to constant light. J Endocrinol 57:7-22
62. Gibson MJ, Krieger DT, Charlton HM, Zimmerman EA, Silverman AJ, Perlow MJ 1984 Mating and pregnancy can occur in genetically hypogonadal mice with preoptic area brain grafts. Science 225: 949-951
63. Schmidt EE, Taylor DS, Prigge JR, Barnett S, Capecchi MR 2000 Illegitimate Cre-dependent chromosome rearrangements in transgenic mouse spermatids. Proc Natl Acad Sci USA 97:13702-13707
64. Srinivas S, Watanabe T, Lin CS, William CM, Tanabe Y, Jessell TM, Costantini F 2001 Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus. BMCDev Biol 1:4
65. Soriano P 1999 Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet 21:70-71
66. Nelson JF, Felicio LS, Randall PK, Sims C, Finch CE 1982 A longitudinal study of extrous cyclicity in aging C57BL/6L mice: I. Cycle frequency, length and vaginal cytology. Biol Reprod 27:327-339
67. DiVall SA, Radovick S, Wolfe A 2007 Egr-1 binds the GnRH promoter to mediate the increase in gene expression by insulin. Mol Cell Endocrinol 270:64-72