Postnatal establishment of allelic gαs silencing as a plausible explanation for delayed onset of parathyroid hormone resistance owing to heterozygous Gαs disruption

Journal of Bone and Mineral Research

Volumn 29, Issue 3, 2014, Pages 749-760

  Turan, Serap ^a,b   Fernandez Rebollo, Eduardo ^a,c   Aydin, Cumhur ^a,d   Zoto, Teuta ^a   Reyes, Monica ^a   Bounoutas, George ^a   Chen, Min ^e   Weinstein, Lee S ^e   Erben, Reinhold G ^f   Marshansky, Vladimir ^a   Bastepe, Murat ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b MARMARA UNIVERSITY SCHOOL OF MEDICINE   (Turkey)

^c HOSPITAL CLÍNIC   (Spain)

^d GULHANE SCHOOL OF MEDICINE   (Turkey)

^e NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

^f UNIVERSITY OF VETERINARY MEDICINE   (Austria)

Author keywords

cyclic AMP; GNAS; imprinting; parathyroid hormone; pseudohypoparathyroidism; renal proximal tubule; stimulatory G protein

Indexed keywords

CYCLIC AMP; GNAS; IMPRINTING; PARATHYROID HORMONE; PSEUDOHYPOPARATHYROIDISM; RENAL PROXIMAL TUBULE; STIMULATORY G PROTEIN;

ALLELES; ANIMALS; DRUG RESISTANCE; FEMALE; GENE SILENCING; GTP-BINDING PROTEIN ALPHA SUBUNITS, GS; HETEROZYGOTE; KIDNEY TUBULES, PROXIMAL; MALE; MICE; MUTATION; PARATHYROID HORMONE;

EID: 84894460206     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.2070     Document Type: Article

References (76)

1. Hirasawa R, Feil R., Genomic imprinting and human disease. Essays Biochem. 2011; 48 (1): 187-200.
2. Barlow DP., Genomic imprinting: a mammalian epigenetic discovery model. Annu Rev Genet. 2011; 45: 379-403.
3. Kozasa T, Itoh H, Tsukamoto T, Kaziro Y., Isolation and characterization of the human Gsa gene. Proc Natl Acad Sci USA. 1988; 85: 2081-5.
4. Weinstein LS, Liu J, Sakamoto A, Xie T, Chen M., Minireview: GNAS: normal and abnormal functions. Endocrinology. 2004; 145 (12): 5459-64.
5. Hayward BE, Moran V, Strain L, Bonthron DT., Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins. Proc Natl Acad Sci USA. 1998; 95: 15475-80.
6. Liu J, Yu S, Litman D, Chen W, Weinstein L., Identification of a methylation imprint mark within the mouse gnas locus. Mol Cell Biol. 2000; 20: 5808-17.
7. Hayward B, Kamiya M, Strain L, et al. The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proc Natl Acad Sci USA. 1998; 95: 10038-43.
8. Hayward B, Bonthron D., An imprinted antisense transcript at the human GNAS1 locus. Hum Mol Genet. 2000; 9: 835-41.
9. Mantovani G, Bondioni S, Locatelli M, et al. Biallelic expression of the Gsalpha gene in human bone and adipose tissue. J Clin Endocrinol Metab. 2004; 89 (12): 6316-9.
10. Hayward B, Barlier A, Korbonits M, et al. Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. J Clin Invest. 2001; 107: R31-6.
11. Mantovani G, Ballare E, Giammona E, Beck-Peccoz P, Spada A., The Gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab. 2002; 87 (10): 4736-40.
12. Liu J, Erlichman B, Weinstein LS., The stimulatory G protein a-subunit Gsa is imprinted in human thyroid glands: implications for thyroid function in pseudohypoparathyroidism types 1A and 1B. J Clin Endocrinol Metabol. 2003; 88 (9): 4336-41.
13. sa gene. Proc Natl Acad Sci USA. 1998; 95: 8715-20.
14. Landis CA, Masters SB, Spada A, Pace AM, Bourne HR, Vallar L., GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature. 1989; 340 (6236): 692-6.
15. Patten JL, Johns DR, Valle D, et al. Mutation in the gene encoding the stimulatory G protein of adenylate cyclase in Albright's hereditary osteodystrophy. N Engl J Med. 1990; 322: 1412-9.
16. Weinstein LS, Gejman PV, Friedman E, et al. Mutations of the Gs alpha-subunit gene in Albright hereditary osteodystrophy detected by denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA. 1990; 87 (21): 8287-90.
17. Davies AJ, Hughes HE., Imprinting in Albright's hereditary osteodystrophy. J Med Genet. 1993; 30: 101-3.
18. Jüppner H, Schipani E, Bastepe M, et al. The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3. Proc Natl Acad Sci USA. 1998; 95: 11798-803.
19. Bringhurst FR, Demay MB, Kronenberg HM., Hormones and disorders of mineral metabolism. In:, Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, editors. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders; 2008.
20. Germain-Lee EL, Schwindinger W, Crane JL, et al. A mouse model of Albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene. Endocrinology. 2005; 146 (11): 4697-709.
21. Ecelbarger CA, Yu S, Lee AJ, Weinstein LS, Knepper MA., Decreased renal Na-K-2Cl cotransporter abundance in mice with heterozygous disruption of the G(s)alpha gene. Am J Physiol. 1999; 277 (2 Pt 2): F235-44.
22. Weinstein LS, Yu S, Ecelbarger CA., Variable imprinting of the heterotrimeric G protein G(s) alpha-subunit within different segments of the nephron. Am J Physiol Renal Physiol. 2000; 278 (4): F507-14.
23. Albright F, Burnett CH, Smith PH, Parson W., Pseudohypoparathyroidism-an example of "Seabright-Bantam syndrome ". Endocrinology. 1942; 30: 922-32.
24. Weinstein LS, Yu S, Warner DR, Liu J., Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting. Endocr Rev. 2001; 22 (5): 675-05.
25. Weinstein LS., The stimulatory G protein alpha-subunit gene: mutations and imprinting lead to complex phenotypes. J Clin Endocrinol Metab. 2001; 86 (10): 4622-6.
26. Linglart A, Gensure RC, Olney RC, Jüppner H, Bastepe M., A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS. Am J Hum Genet. 2005; 76 (5): 804-14.
27. Linglart A, Carel JC, Garabedian M, Le T, Mallet E, Kottler ML., GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance. J Clin Endocrinol Metab. 2002; 87 (1): 189-97.
28. Riepe FG, Ahrens W, Krone N, et al. Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene. Eur J Endocrinol. 2005; 152 (4): 515-9.
29. Yu D, Yu S, Schuster V, Kruse K, Clericuzio CL, Weinstein LS., Identification of two novel deletion mutations within the Gs alpha gene (GNAS1) in Albright hereditary osteodystrophy. J Clin Endocrinol Metab. 1999; 84 (9): 3254-9.
30. Lebrun M, Richard N, Abeguile G, et al. Progressive osseous heteroplasia: a model for the imprinting effects of GNAS inactivating mutations in humans. J Clin Endocrinol Metab. 2010; 95 (6): 3028-38.
31. Thiele S, de Sanctis L, Werner R, et al. Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction. Hum Mutat. 2011; 32 (6): 653-60.
32. Fischer JA, Egert F, Werder E, Born W., An inherited mutation associated with functional deficiency of the alpha-subunit of the guanine nucleotide-binding protein Gs in pseudo- and pseudopseudohypoparathyroidism. J Clin Endocrinol Metab. 1998; 83 (3): 935-8.
33. Patra S, Singh V, Pemde HK, Chandra J., Case series of neonatal hypocalcemia due to pseudohypoparathyroidism. J Pediatr Endocrinol Metab. 2010; 23 (10): 1073-5.
34. Khadilkar A, Mughal MZ, Hanumante N, et al. Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers. Arch Dis Child. 2009; 94 (12): 932-7.
35. Shalitin S, Davidovits M, Lazar L, Weintrob N., Clinical heterogeneity of pseudohypoparathyroidism: from hyper- to hypocalcemia. Horm Res. 2008; 70 (3): 137-44.
36. Lee CT, Tsai WY, Tung YC, Tsau YK., Transient pseudohypoparathyroidism as a cause of late-onset hypocalcemia in neonates and infants. J Formos Med Assoc. 2008; 107 (10): 806-10.
37. Narang M, Salota R, Sachdev SS., Neonatal pseudohypoparathyroidism. Indian J Pediatr. 2006; 73 (1): 97-8.
38. Sajitha S, Krishnamoorthy PN, Shenoy UV., Pseudohypoparathyroidism in newborn-a rare presentation. Indian Pediatr. 2003; 40 (1): 47-9.
39. Manzar S., Transient pseudohypoparathyroidism and neonatal seizure. J Trop Pediatr. 2001; 47 (2): 113-4.
40. Kruse K, Kustermann W., Evidence for transient peripheral resistance to parathyroid hormone in premature infants. Acta Paediatr Scand. 1987; 76 (1): 115-8.
41. Mallet E, Basuyau JP, Brunelle P, Devaux AM, Fessard C., Neonatal parathyroid secretion and renal receptor maturation in premature infants. Biol Neonate. 1978; 33 (5-6): 304-8.
42. Williamson CM, Ball ST, Nottingham WT, et al. A cis-acting control region is required exclusively for the tissue-specific imprinting of Gnas. Nat Genet. 2004; 36 (8): 894-9.
43. Chen M, Gavrilova O, Liu J, et al. Alternative Gnas gene products have opposite effects on glucose and lipid metabolism. Proc Natl Acad Sci USA. 2005; 102 (20): 7386-91.
44. Bounoutas GS, Tawfeek H, Fröhlich LF, Chung UI, Abou-Samra AB., Impact of impaired receptor internalization on calcium homeostasis in knock-in mice expressing a phosphorylation-deficient parathyroid hormone (PTH)/PTH-related peptide receptor. Endocrinology. 2006; 147 (10): 4674-9.
45. Liu Z, Segawa H, Aydin C, et al. Transgenic overexpression of the extra-large Gs{alpha} variant XL{alpha}s enhances Gs{alpha}-mediated responses in the mouse renal proximal tubule in vivo. Endocrinology. 2011; 152 (4): 1222-33.
46. Hurtado-Lorenzo A, Skinner M, El Annan J, et al. V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway. Nat Cell Biol. 2006; 8 (2): 124-36.
47. Walden U, Weissortel R, Corria Z, et al. Stimulatory guanine nucleotide binding protein subunit 1 mutation in two siblings with pseudohypoparathyroidism type 1a and mother with pseudopseudohypoparathyroidism. Eur J Pediatr. 1999; 158 (3): 200-3.
48. Gelfand IM, Eugster EA, Dimeglio LA., Presentation and clinical progression of pseudohypoparathyroidism with multi-hormone resistance and Albright hereditary osteodystrophy: a case series. J Pediatr. 2006; 149 (6): 877-80.
49. Long DN, McGuire S, Levine MA, Weinstein LS, Germain-Lee EL., Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007; 92 (3): 1073-9.
50. Tomlinson S, Hendy GN, O'Riordan JH., A simplified assessment of response to parathyroid hormone in hypoparathyroid patients. Lancet. 1976; 1 (7950): 62-4.
51. Kruse K, Kracht U., A simplified diagnostic test in hypoparathyroidism and pseudohypoparathyroidism type I with synthetic 1-38 fragment of human parathyroid hormone. Eur J Pediatr. 1987; 146 (4): 373-7.
52. Tomlinson S, Barling PM, Albano JD, Brown BL, O'Riordan JL., The effects of exogenous parathyroid hormone on plasma and urinary adenosine 3', 5'-cyclic monophosphate in man. Clin Sci Mol Med. 1974; 47 (5): 481-92.
53. Albright F, Forbes AP, Henneman PH., Pseudo-pseudohypoparathyroidism. Trans Assoc Am Physicians. 1952; 65: 337-50.
54. Werder EA, Fischer JA, Illig R, et al. Pseudohypoparathyroidism and idiopathic hypoparathyroidism: relationship between serum calcium and parathyroid hormone levels and urinary cyclic adenosine-3',5'-monophosphate response to parathyroid extract. J Clin Endocrinol Metab. 1978; 46 (6): 872-9.
55. Lubell T, Garzon M, Anyane Yeboa K, Shah B., A novel mutation causing pseudohypoparathyroidism 1A with congenital hypothyroidism and osteoma cutis. J Clin Res Pediatr Endocrinol. 2009; 1 (5): 244-7.
56. Fernandez-Rebollo E, Maeda A, Reyes M, et al. Loss of XLalphas (extra-large alphas) imprinting results in early postnatal hypoglycemia and lethality in a mouse model of pseudohypoparathyroidism Ib. Proc Natl Acad Sci USA. 2012; 109 (17): 6638-43.
57. Zierold C, Mings JA, DeLuca HF., Parathyroid hormone regulates 25-hydroxyvitamin D(3)-24-hydroxylase mRNA by altering its stability. Proc Natl Acad Sci USA. 2001; 98 (24): 13572-6.
58. Kumar R, Tebben PJ, Thompson JR., Vitamin D and the kidney. Arch Biochem Biophys. 2012; 523 (1): 77-86.
59. Zheng H, Radeva G, McCann JA, Hendy GN, Goodyer CG., Gas transcripts are biallelically expressed in the human kidney cortex: implications for pseudohypoparathyroidism type Ib. J Clin Endocrinol Metab. 2001; 86 (10): 4627-9.
60. Cattanach BM, Peters J, Ball S, Rasberry C., Two imprinted gene mutations: three phenotypes. Hum Mol Genet. 2000; 9 (15): 2263-73.
61. Fröhlich LF, Mrakovcic M, Steinborn R, Chung UI, Bastepe M, Juppner H., Targeted deletion of the Nesp55 DMR defines another Gnas imprinting control region and provides a mouse model of autosomal dominant PHP-Ib. Proc Natl Acad Sci USA. 2010; 107 (20): 9275-80.
62. Eaton SA, Williamson CM, Ball ST, et al. New mutations at the imprinted Gnas cluster show gene dosage effects of Gsalpha in postnatal growth and implicate XLalphas in bone and fat metabolism but not in suckling. Mol Cell Biol. 2012; 32 (5): 1017-29.
63. Levine MA, Jap TS, Hung W., Infantile hypothyroidism in two sibs: an unusual presentation of pseudohypoparathyroidism type Ia. J Pediatr. 1985; 107 (6): 919-22.
64. Weisman Y, Golander A, Spirer Z, Farfel Z., Pseudohypoparathyroidism type 1a presenting as congenital hypothyroidism. J Pediatr. 1985; 107 (3): 413-5.
65. Yokoro S, Matsuo M, Ohtsuka T, Ohzeki T., Hyperthyrotropinemia in a neonate with normal thyroid hormone levels: the earliest diagnostic clue for pseudohypoparathyroidism. Biol Neonate. 1990; 58 (2): 69-72.
66. Xie T, Plagge A, Gavrilova O, et al. The alternative stimulatory G protein alpha-subunit XLalphas is a critical regulator of energy and glucose metabolism and sympathetic nerve activity in adult mice. J Biol Chem. 2006; 281 (28): 18989-99.
67. Prickett AR, Oakey RJ., A survey of tissue-specific genomic imprinting in mammals. Mol Genet Genomics. 2012; 287 (8): 621-30.
68. Gould TD, Pfeifer K., Imprinting of mouse Kvlqt1 is developmentally regulated. Hum Mol Genet. 1998; 7 (3): 483-7.
69. Paulsen M, Davies KR, Bowden LM, et al. Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5. Hum Mol Genet. 1998; 7 (7): 1149-59.
70. Sanz LA, Chamberlain S, Sabourin JC, et al. A mono-allelic bivalent chromatin domain controls tissue-specific imprinting at Grb10. EMBO J. 2008; 27 (19): 2523-32.
71. Davies SM., Developmental regulation of genomic imprinting of the IGF2 gene in human liver. Cancer Res. 1994; 54 (10): 2560-2.
72. Zhuang Z, Marshansky V, Breton S, Brown D., Is caveolin involved in normal proximal tubule function? Presence in model PT systems but absence in situ. Am J Physiol Renal Physiol. 2011; 300 (1): F199-206.
73. Bastepe M, Gunes Y, Perez-Villamil B, Hunzelman J, Weinstein LS, Jüppner H., Receptor-mediated adenylyl cyclase activation through XLalphas, the extra-large variant of the stimulatory G protein alpha-subunit. Mol Endocrinol. 2002; 16 (8): 1912-9.
74. Linglart A, Mahon MJ, Kerachian MA, et al. Coding GNAS mutations leading to hormone resistance impair in vitro agonist- and cholera toxin-induced adenosine cyclic 3',5'-monophosphate formation mediated by human XLas. Endocrinology. 2006; 147 (5): 2253-62.
75. Gensure RC, Gardella TJ, Jüppner H., Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochem Biophys Res Commun. 2005; 328 (3): 666-78.
76. Gesty-Palmer D, Chen M, Reiter E, et al. Distinct beta-arrestin- and G protein-dependent pathways for parathyroid hormone receptor-stimulated ERK1/2 activation. J Biol Chem. 2006; 281 (16): 10856-64.