Abnormalities in the genes encoding Pit-1 and Prop-1 have been reported to cause combined pituitary hormone deficiency (CPHD) in mice and humans. In dogs, a similar phenotype has been described in the German shepherd breed. We have previously reported that the Pit-1 gene (POU1F1) is not mutated in affected German shepherd dogs. In this study, we report the isolation and mapping of the canine Prop-1 gene (PROP1), and we assessed the involvement of PROP1 in German shepherd dog dwarfism. The canine PROP1 gene was found to contain three exons, encoding a 226 amino acid protein. The deduced amino acid sequence was 79% and 84% homologous with the mouse and human Prop-1 protein, respectively. Using fluorescence in situ hybridization, PROP1 was mapped to canine chromosome 11. Further mapping with a canine radiation hybrid panel showed co-localization with the polymorphic DNA marker AHT137. Sequence analysis of genomic DNA from dwarf German shepherd dogs revealed no alterations in the PROP1 gene. Moreover, linkage analysis of AHT137 revealed no co-segregation between the PROP1 locus and the CPHD phenotype, excluding this gene as candidate for canine CPHD and providing a new spontaneous model of hypopituitarism.   

1.
Aguirre GD, Baldwin V, Weeks KM, Acland GM, Ray K: Frequency of the codon 807 mutation in the cGMP phosphodiesterase beta-subunit gene in Irish setters and other dog breeds with hereditary retinal degeneration. J Hered 90:143–147 (1999).
2.
Andresen E, Willeberg P: Pituitary dwarfism in German shepherd dogs: additional evidence of simple, autosomal recessive inheritance. Nord vet Med 28:481–486 (1976).
3.
Breen M, Bullerdiek J, Langford CF: The DAPI banded karyotype of the domestic dog (Canis familiaris) generated using chromosome specific paint probes. Chrom Res 7:401–406 (1999a).
4.
Breen M, Langford CF, Carter NP, Holmes NG, Dickens HF, Thomas R, Suter N, Ryder EJ, Pope M, Binns MM: FISH mapping and identification of canine chromosomes. J Hered 90:27–30 (1999b).
5.
Flück C, Deladoey J, Rutishauser K, Eblé A, Marti U, Wu W, Mullis PE: Phenotypic variability in familial combined pituitary hormone deficiency caused by a Prop-1 gene mutation resulting in the substitution of Arg→Cys at codon 120 (R120C). J clin Endocrin Metab 83:3727–3734 (1998).
6.
Hamann F, Kooistra HS, Mol JA, Gottschalk S, Bartels T, Rijnberk A: Pituitary function and morphology in two German shepherd dogs with congenital dwarfism. Vet Rec 144:644–646 (1999).
7.
Holmes NG, Dickens HF, Parker HL, Binns MM, Mellersh CS, Sampson J: Eighteen canine microsatellites. Anim Genet 26:132–133 (1995).
8.
Kooistra HS, Voorhout G, Selman PJ, Rijnberk A: Progestin-induced growth hormone (GH) production in the treatment of dogs with congenital GH deficiency. Domest Anim Endocrin 15:93–102 (1998).
9.
Lantinga-van Leeuwen IS, Mol JA, Kooistra HS, Rijnberk A, Breen M, Renier C, van Oost BA: Cloning of the canine gene encoding transcription factor Pit-1 and mutation analysis in a canine model of pituitary dwarfism. Mammal Genome (2000, in press).
10.
Li R, Mignot E, Faraco J, Kodatani H, Cantanese JJ, Zhao BH, Lin X, Hinton L, Ostrander EA, Patterson DF, de Jong P: Construction and characterization of an eightfold redundant dog genomic bacterial artificial chromosome library. Genomics 58:9–17 (1999).
11.
Li S, Crenshaw III EB, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG: Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene Pit-1. Nature 347:528–533 (1990).
12.
Matise TC, Perlin M, Chakravarti A: Automated construction of genetic linkage maps using an expert system (MultiMap): a human genome linkage map. Nature Genet 6:384–390 (1994).
13.
Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acid Res 16:1215 (1988).
14.
Mol JA, van Garderen E, Selman PJ, Wolfswinkel J, Rijnberk A, Rutteman GR: Growth hormone mRNA in mammary gland tumors of dogs and cats. J clin Invest 95:2028–2034 (1995).
15.
Pfäffle R, Kim C, Otten B, Wit JM, Eiholzer U, Heimann G, Parks J: Pit-1: clinical aspects. Hormone Res 45(Suppl 1):25–28 (1996).
16.
Priat C, Hitte C, Vignaux F, Renier C, Jiang Z, Jouquand S, Chéron A, André C, Galibert F: A whole-genome radiation hybrid map of the dog genome. Genomics 54:361–378 (1998).
17.
Shapiro MB, Senapathy P: RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucl Acids Res 15:7155–7174 (1987).
18.
Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Andersen B, Beamer WG, Rosenfeld MG: Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327–333 (1996).
19.
Treier M, Gleiberman AS, O’Connell SM, Szeto DP, McMahon JA, McMahon AP, Rosenfeld MG: Multistep signaling requirements for pituitary organogenesis in vivo. Genes Dev 12:1691–1704 (1998).
20.
Vignaux F, Hitte C, Priat C, Chuat JC, Galibert F: Construction and optimization of a dog whole genome radiation hybrid panel. Mammal Genome 10:888–894 (1999a).
21.
Vignaux F, Priat C, Jouquand S, Hitte C, Jiang Z, Chéron A, Renier C, André C, Galibert F: Toward a dog radiation hybrid map. J Hered 90:62–67 (1999b).
22.
Watkins-Chow DE, Camper SA: How many homeobox genes does it take to make a pituitary gland? Trends Genet 14:284–290 (1998).
23.
Wu W, Cogan JD, Pfäffle RW, Dasen JS, Frisch H, O’Connell SM, Flynn SE, Brown MR, Mullis PE, Parks JS, Phillips III JA, Rosenfeld MG: Mutations in Prop-1 cause familial combined pituitary hormone deficiency. Nature Genet 18:147–149 (1998).
© 2000 S. Karger AG, Basel
2000
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.