J. Anim Sci. 2007. 85:598-603. doi:10.2527/jas.2006-324
© 2007 American Society of Animal Science
Mutations in BMPR-IB and BMP-15 genes are associated with litter size in Small Tailed Han sheep (Ovis aries)1
M. X. Chu*,2,
Z. H. Liu
,
C. L. Jiao,
Y. Q. He,
L. Fang*,
S. C. Ye*,
G. H. Chen and
J. Y. Wang
* Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100094, China; and
and
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
 |
Abstract
|
|---|
The Small Tailed Han is a prolific local sheep breed in China. The bone morphogenetic protein receptor IB (BMPR-IB) gene, which affects the fecundity of Booroola Merino sheep, and the bone morphogenetic protein 15 (BMP-15) gene, which affects the fecundity of Inverdale, Hanna, Belclare, Cambridge, and Lacaune sheep, were studied as candidate genes associated with the prolificacy of Small Tailed Han sheep. Single nucleotide polymorphisms of BMPR-IB and BMP-15 genes were detected in Small Tailed Han ewes (n = 188) by PCR-RFLP. The combined effect of the 2 genes on the prolificacy of Small Tailed Han sheep was studied. The results indicated that the same FecB mutation (Q249R) occurred in the BMPR-IB gene in Small Tailed Han ewes as found in Booroola Merino ewes. The Small Tailed Han ewes with genotypes FecBB/FecBB and FecBB/FecB+ had 1.40 (P < 0.01) and 1.11 (P < 0.01) more lambs, respectively, than those with genotype FecB+/FecB+. The same FecXG mutation (Q239Ter) of the BMP-15 gene was found in Small Tailed Han ewes as in Belclare and Cambridge ewes. The Small Tailed Han ewes with the heterozygous mutant FecXG/FecX+ had 0.55 (P < 0.01) more lambs than those with the wild-type FecX+/FecX+. The Small Tailed Han ewes carrying mutations in both BMPR-IB and BMP-15 genes had greater litter size than those with either mutation alone. In view of our results, marker-assisted selection using both BMPR-IB and BMP-15 genes is warranted to increase litter size in sheep and will be of considerable economic value to sheep producers.
Key Words: bone morphogenetic protein 15 gene • bone morphogenetic protein receptor IB gene • prolificacy • sheep
|
INTRODUCTION
|
|---|
The Booroola gene (FecB) was the first major gene for prolificacy identified in sheep. The FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22–23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene, which encodes a member of the transforming growth factor ß (TGFß) receptor family (Mulsant et al., 2001
; Wilson et al., 2001). A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was associated fully with the hyperprolific phenotype of Booroola ewes (Mulsant et al., 2001; Souza et al., 2001; Wilson et al., 2001).
Bone morphogenetic protein 15 (BMP-15) is a growth factor and a member of the TGFß superfamily that is specifically expressed in oocytes. The sheep BMP-15 gene maps to the X chromosome (Galloway et al., 2000). Bone morphogenetic protein 15 regulates granulosa cell proliferation and differentiation by promoting granulosa cell mitosis, suppressing follicle-stimulating hormone receptor expression, and stimulating kit ligand expression, all of which play a pivotal role in female fertility in mammals (Otsuka et al., 2000, 2001; Juengel et al., 2002; Otsuka and Shimasaki, 2002a,b; Moore and Shimasaki, 2005). The FecXG mutation (Q239Ter) in the BMP-15 gene was associated with increased ovulation rate and sterility in Cambridge and Belclare sheep (Hanrahan et al., 2004).
The Small Tailed Han is a prolific local sheep breed in China. The mean litter size was 2.61 (Tu, 1989) and 2.65 (Wang et al., 1990) in Small Tailed Han sheep of Shandong Province, China. To date, there are no reports about the combined effect of the BMPR-IB and BMP-15 genes on litter size in sheep.
The objectives of the current study were 1) to detect the single nucleotide polymorphisms of the 2 genes by PCR-RFLP and sequencing, and 2) to investigate the combined effect of the 2 genes on prolificacy of Small Tailed Han sheep.
|
MATERIALS AND METHODS
|
|---|
Animals
All experimental procedures were performed according to authorization granted by the Chinese Ministry of Agriculture. All procedures involving animals were approved by the animal care and use committee at the respective institution where the experiment was conducted. All procedures involving animals were approved and authorized by the Chinese Ministry of Agriculture.
Venous jugular blood samples (10 mL per ewe) were collected from 188 Small Tailed Han ewes lambed in 2004, along with data on litter size in the first, second, or third parity on the Jia-xiang Breeding Sheep Farm in Shandong Province, China, using acid citrate dextrose as an anticoagulant. Genomic DNA was extracted from whole blood by the phenol-chloroform method, then dissolved in TE buffer (10 mM Tris-HCl and 1 mM EDTA, pH 8.0), and kept at –20°C.
The 188 ewes were chosen at random and were the progeny of 8 rams. Because the 8 rams were sold, their blood was not collected and they were not genotyped. No selection on litter size or other fertility traits was performed in the flock over previous years. Lambing seasons consisted of 3-mo groups beginning with March through May as season 1 (spring), June through August as season 2 (summer), September through November as season 3 (autumn), and December through February as season 4 (winter).
Detection of the FecB and the FecXG Mutations
A primer pair was designed to detect single nucleotide polymorphisms in exon 6 of the BMPR-IB gene in prolific Small Tailed Han sheep by PCR-RFLP. Primers amplified a 140-bp band. After digestion with Ava II (New England Biolabs, Beverly, MA), the BB animals had a 110-bp band, the B+ animals had 140- and 110-bp bands, and the ++ animals had a 140-bp band (Wilson et al., 2001). The primer sequences were as follows:
Forward:
5'-GTCGCTATGGGGAAGTTTGGATG-3'; and
Reverse:
5'-CAAGATGTTTTCATGCCTCATCAACACGGTC-3'.
A primer pair was also designed to detect SNP of the BMP-15 gene with Hinf I (Promega, Madison, WI). Primers amplified a 141-bp band (Hanrahan et al., 2004). The primer sequences were as follows:
Forward:
5'-CACTGTCTTCTTGTTACTGTATTTCAATGAGAC-3';
and
Reverse:
5'-GATGCAATACTGCCTGCTTG-3'.
Polymerase chain reactions were carried out in a 25-µL reaction mixture containing approximately 2.5 µL of 10x PCR buffer [50 mM KCl, 10 mM Tris-HCl (pH 8.0), 0.1% Triton X-100], 1.5 mM of MgCl2, 200 µM of each dNTP, 2 µM of each primer, 50 ng of ovine genomic DNA, and 1 U of Taq DNA polymerase (Promega, Madison, WI). The amplification conditions for primers of the BMPR-IB gene were as follows: denaturation at 94°C for 5 min; followed by 35 cycles of denaturation at 94°C for 30 s, annealing at 60°C for 30 s, and extension at 72°C for 30 s; with a final extension at 72°C for 5 min, on a Mastercycler 5333 (Eppendorf AG, Hamburg, Germany). The amplification conditions for primers of the BMP-15 gene were as follows: denaturation at 95°C for 5 min; followed by 30 cycles of denaturation at 95°C for 45 s, annealing at 63°C for 45 s, and extension at 72°C for 1 min; with a final extension at 72°C for 10 min on a Mastercycler 5333 (Eppendorf AG).
The PCR products of 5 µL were digested separately with 10 U of Ava II (New England Biolabs) and 10 U of Hinf I (Promega) at 37°C for 4 h in a 20-µL reaction mixture. The resultant fragments were separated by electrophoresis on 3% agarose gels (Promega). The gels were visualized with ethidium bromide, photographed, and analyzed using an AlphaImager 2200 and 1220 Documentation and Analysis Systems (Alpha Innotech Corporation, San Leandro, CA).
Statistical Analysis
Least squares analysis of variance was conducted for BMPR-IB genotypes, BMP-15 genotypes, and their combined genotypes. Therefore, the following statistical model was fitted to compare differences in litter size among different genotypes:
where y is the phenotypic value of litter size; µ is the population mean; LS is the fixed lambing season effect (LS = 1, 2, 3, or 4); P is the fixed parity effect (P = 1, 2, or 3); G1 is the fixed effect for BMPR-IB genotypes; G2 is the fixed effect for BMP-15 genotypes; G1G2 is the fixed interaction effect for BMPR-IB and BMP-15 combined genotypes; s is the random sire effect (s = 1, 2, 3, 4, 5, 6, 7, or 8); and e is the random error effect of each observation. Analysis was performed using the GLM procedure (SAS Inst. Inc., Cary, NC). Mean separation procedures were performed using a least significant difference test.
|
RESULTS
|
|---|
Detection of the FecB Mutation of the BMPR-IB Gene
Three genotypes, BB (110 bp/110 bp), B+ (110 bp/140 bp), and ++ (140 bp/140 bp), were detected in Small Tailed Han sheep (Figure 1). Sequencing verified the presence (or absence) of the polymorphic Ava II cleavage site as assessed by agarose gel electrophoresis. The nucleotide sequence obtained from genotype BB was identical to the wild-type ++, except for an A
G transition at base 746 of the coding region of the BMPR-IB gene. This mutation results in a change in the amino acid coded from a glutamine in the wild-type to an arginine in the BB genotype (CAGCGG, Q249R). The results indicated that Small Tailed Han ewes carried the same FecB mutation of the BMPR-IB gene as found in Booroola Merino ewes (Mulsant et al., 2001; Souza et al., 2001; Wilson et al., 2001).
View larger version (36K):
[in this window]
[in a new window]
|
Figure 1. Image of PCR product of the FecB mutation of the BMPR-IB gene digested with Ava II. M = SD011 DNA marker. The wild-type allele (+) is 140 bp, and the mutant allele (B) is 110 bp. Lanes 2, 7, and 8 = the B+ genotype (heterozygote); lanes 1 and 6 = the ++ genotype (wild-type); lanes 3, 4, and 5 = the BB genotype (homozygous mutant).
|
|
Detection of the FecXG Mutation of the BMP-15 Gene
Two genotypes, ++ (111 bp/111 bp) and G+ (141 bp/111 bp), were detected in Small Tailed Han sheep (Figure 2). Forward and reverse sequencing identified the Hinf I RFLP polymorphism as a C/T single nucleotide change at position 718 of the BMP-15 gene. The nucleotide sequence obtained from genotype G+ was identical to the wild-type ++, except for a CT change at nucleotide 718 of the BMP-15 gene. This mutation introduces a premature stop codon in place of glutamic acid at amino acid residue 239 of the unprocessed protein, which presumably results in complete loss of BMP-15 function (CAGTAG, Q239Ter). The results indicated that Small Tailed Han ewes carried the same FecXG mutation of the BMP-15 gene as found in Belclare and Cambridge ewes (Hanrahan et al., 2004).
View larger version (53K):
[in this window]
[in a new window]
|
Figure 2. Image of PCR product of the FecXG mutation of the BMP-15 gene digested with Hinf I. M = SD011 DNA marker. The wild-type allele (+) is 111 bp, and the mutant allele (G) is 141 bp. Lanes 1 to 4 = the G+ genotype; lanes 5 to 8 = the ++ genotype.
|
|
Allelic and Genotypic Frequencies in Small Tailed Han Sheep
Allelic and genotypic frequencies of the FecB mutation of the BMPR-IB gene and the FecXG mutation of the BMP-15 gene are presented in Table 1. For the BMPR-IB gene, frequencies of genotypes BB, B+, and ++ were 0.52, 0.42, and 0.06, respectively. For the BMP-15 gene, frequencies of genotypes G+, ++, and GG were 0.60, 0.40, and 0.00, respectively.
View this table:
[in this window]
[in a new window]
|
Table 1. Allelic and genotypic frequencies of the FecB mutation of the BMPR-IB gene and the FecXG mutation of the BMP-15 gene in Small Tailed Han ewes1
|
|
Combined genotypic frequencies of the FecB and FecXG mutations are presented in Table 2. Combined genotype BBG+ had the highest frequency (0.29), whereas ++G+ and ++++ had the lowest frequency (0.03). It should be noted that these allelic and genotypic frequencies are based on a sample of fertile ewes, rather than the population as a whole, because these polymorphisms are associated with infertility, and because one of them is sex-linked. In addition, the use of only 8 sires limits the ability to make inferences about the entire population based on these sample data.
Effects of BMPR-IB and BMP-15 Genes on Litter Size in Small Tailed Han Sheep
Litter size in Small Tailed Han sheep was significantly influenced by BMPR-IB and BMP-15 genotypes (P = 0.0012 and 0.0025, respectively). In addition, a highly significant interaction was observed between the BMPR-IB and BMP-15 genotypes (P = 0.0063).
The least squares means and SE for litter size of different genotypes in Small Tailed Han sheep are given in Table 3. The Small Tailed Han ewes with genotypes BB and B+ had 1.40 (P < 0.01) and 1.11 (P < 0.01) more lambs, respectively, than those with genotype ++. The Small Tailed Han ewes with the heterozygous mutant G+ genotype had 0.55 (P < 0.01) more lambs than those with the wild-type ++ genotype. The Small Tailed Han ewes carrying mutations in both BMPR-IB and BMP-15 genes had greater litter size than those with either mutation alone. The effect of the BMPR-IB gene mutation was greater than that of the BMP-15 gene mutation on litter size in Small Tailed Han ewes.
View this table:
[in this window]
[in a new window]
|
Table 3. Least squares means and SE for litter size of different BMPR-IB and BMP-15 genotypes in Small Tailed Han sheep
|
|
|
DISCUSSION
|
|---|
The FecB mutation is present in Booroola Merino (Australia; Mulsant et al., 2001; Souza et al., 2001; Wilson et al., 2001), Garole (India; Davis et al., 2002), Javanese (Indonesia; Davis et al., 2002), Small Tailed Han (China; Liu et al., 2003; Wang et al., 2003a; Jia et al., 2005; Yan et al., 2005; Davis et al., 2006), and Hu (China) sheep (Wang et al., 2003a, b, 2005; Yan et al., 2005; Davis et al., 2006; Guan et al., 2006). This study also showed that the FecB mutation is present in Small Tailed Han sheep (China). Therefore, these 5 ovine breeds may share a common ancestor.
In sheep, 5 different point mutations [FecXI (Inverdale), Galloway et al., 2000; FecXH (Hanna) Galloway et al., 2000; FecXL (Lacaune), Bodin et al., 2003; FecXG (Belclare and Cambridge), Hanrahan et al., 2004; and FecXB (Belclare), Hanrahan et al., 2004] have been identified in the BMP-15 gene, each having a major effect on ovulation rate. Ewes heterozygous for any one of these BMP-15 mutations have increased ovulation rates, whereas homozygous ewes are sterile due to a failure of normal ovarian follicular development (Davis et al., 1992; Braw-Tal et al., 1993; Galloway et al., 2000; Bodin et al., 2003; Hanrahan et al., 2004). Crossing FecXI and FecXH sheep produces FecXI/FecXH infertile females, which are phenotypically indistinguishable from FecXI/FecXI females (Davis et al., 1995). Belclare heterozygous FecXG/FecXB ewes were also sterile (Hanrahan et al., 2004). None of Small Tailed Han and Hu sheep carried the FecXB or FecXH mutation (Liu et al., 2003; Chu et al., 2005a,b). None of Garole, Javanese, Small Tailed Han, or Hu sheep had the FecXI mutation (Davis et al., 2002; Liu et al., 2003; Chu et al., 2005a; Wang et al., 2005; Davis et al., 2006). The prolific Hu sheep did not have the FecXG mutation (Chu et al., 2005b). The current study and Chu et al. (2005b) indicated that Small Tailed Han sheep had the same FecXG mutation (C718T) of the BMP-15 gene as Belclare and Cambridge ewes. It is unknown whether prolific Small Tailed Han and Hu sheep carry the FecXL mutation. To our knowledge, this is the first case in which the same FecXG mutation has been found in apparently unrelated breeds (Belclare/Cambridge and Small Tailed Han). Regarding the FecXG mutation, it would be very interesting to compare the local haplotype around the mutation, as well as to compare genetic distances between Belclare/Cambridge and Small Tailed Han sheep, using other markers. This would help to determine whether mutant animals in these 2 breeds derive from a unique mutational event or whether the mutation occurred twice independently.
No GG ewes were detected among the 188 Small Tailed Han ewes in this study. Hanrahan et al. (2004) reported that GG ewes were sterile. Ewes of this genotype were not detected in 83 Belclare ewes, whereas 12 GG ewes were detected in 129 Cambridge ewes (Hanrahan et al., 2004). Possible reasons no GG ewes were observed in this study include: (i) GG ewes exist in the Small Tailed Han breed, but the method used to select ewes for this study (only ewes with litter records were used) excluded all infertile GG ewes, and (ii) GG ewes do not exist in the Small Tailed Han breed. If GG ewes exist in Small Tailed Han sheep, 60% of fertile Small Tailed Han ewes are G+, and matings are at random, infertility must be associated with GG ewes throughout this breed. Because there are no reports of infertility among Small Tailed Han ewes to date, we hypothesize that there were no GG ewes in the Small Tailed Han breed, as was the case in Belclare sheep. Mating of G+ rams and G+ ewes, extensive sampling, and DNA analysis would be required to verify this hypothesis. Such a study would have important implications for the sheep industry.
The BMP-15 binds to BMPR-IB and to BMPR-II (Moore et al., 2003). The interaction between the Booroola and Inverdale mutations appears to be multiplicative in that animals that are heterozygous for both the Booroola mutation and the Inverdale mutation have ovulation rates greater than the increase expected for an additive effect alone (Davis et al., 1999). The Small Tailed Han ewes carrying mutations in both BMPR-IB and BMP-15 genes had greater litter size than those with either mutation alone in the current study. To our knowledge, the Small Tailed Han sheep is the third sheep breed where mutations in 2 different genes have been shown to segregate, after the Belclare/Cambridge (GDF-9 and BMP-15; Hanrahan et al., 2004) and the Lacaune sheep (FecL and BMP-15; Bodin et al., 2003), and the first where the effect of the different genotypes on litter size was determined. Because of a low number of ++ animals at the FecB locus, it is difficult to determine whether the combined effect of both mutations is additive or synergistic. This topic is worthy of further study. The present results have important implications for the sheep industry because Small Tailed Han flocks will have ewes of widely different levels of prolificacy and ewes homozygous for FecXG will be sterile.
The regulatory mechanism of BMPR-IB and BMP-15 in prolific Small Tailed Han and Hu sheep deserves further study. Ongoing investigations into the basis of the prolific phenotype of Small Tailed Han and Hu ewes are likely to reveal further insights into the events controlling follicle and oocyte development.
|
IMPLICATIONS
|
|---|
The Small Tailed Han is a prolific local sheep breed in China. The Small Tailed Han ewes in this study carried the same FecB mutation (Q249R) of the bone morphogenetic protein receptor IB (BMPR-IB) gene as found in Booroola Merino ewes and the same FecXG mutation (Q239Ter) of the bone morphogenetic protein 15 (BMP-15) gene as found in Belclare and Cambridge ewes. Moreover, Small Tailed Han ewes carrying mutations in both BMPR-IB and BMP-15 genes had greater litter size than those with either mutation alone. In view of our results, marker-assisted selection using both BMPR-IB and BMP-15 genes is warranted to increase litter size in sheep and will be of considerable economic value to sheep producers.
|
Footnotes
|
|---|
1 This research was supported by National Key Basic Research and Development Program of China (No. 2006CB102105), by National Natural Science Foundation of China (No. 30300248 and No. 30140004), and by Beijing Science and Technology Program of China (No. Y0705003041131). 
2 Corresponding author: mxchu{at}263.net
Received for publication May 19, 2006.
Accepted for publication October 5, 2006.
|
LITERATURE CITED
|
|---|
Bodin, L., F. Lecerf, C. Pisselet, M. San Cristhal, M. Bibe, and P. Mulsant. 2003. How many mutations are associated with increased ovulation rate and litter size in progeny of Lacaune meat sheep? Pages 2–11 in Proc. Int. Workshop on Major Genes and QTL in Sheep and Goats. INRA, Toulouse, France.
Braw-Tal, R., K. P. McNatty, P. Smith, D. A. Heath, N. L. Hudson, D. J. Philips, B. J. McLeod, and G. H. Davis. 1993. Ovaries of ewes homozygous for the X-linked Inverdale gene (FecXI) are devoid of secondary and tertiary follicles but contain many abnormal structures. Biol. Reprod. 49:895–907.[Abstract]
Chu, M. X., R. Cheng, G. H. Chen, L. Fang, and S. C. Ye. 2005a. Study on bone morphogenetic protein 15 as a candidate gene for prolificacy of Small Tailed Han sheep and Hu sheep. J. Anhui Agric. Univ. 32:278–282.
Chu, M. X., L. H. Sang, J. Y. Wang, L. Fang, and S. C. Ye. 2005b. Study on BMP15 and GDF9 as candidate genes for prolificacy of Small Tailed Han sheep. Acta Genetica Sinica 32:38–45.
Davis, G. H., L. Balakrishnan, I. K. Ross, T. Wilson, S. M. Galloway, B. M. Lumsden, J. P. Hanrahan, M. Mullen, X. Z. Mao, G. L. Wang, Z. S. Zhao, Y. Q. Zeng, J. J. Robinson, A. P. Mavrogenis, C. Papachristoforou, C. Peter, R. Baumung, P. Cardyn, I. Boujenane, N. E. Cockett, E. Eythorsdottir, J. J. Arranz, and D. R. Notter. 2006. Investigation of the Booroola (FecB) and Inverdale (FecXI) mutations in 21 prolific breeds and strains of sheep sampled in 13 countries. Anim. Reprod. Sci. 92:87–96.[CrossRef][Medline]
Davis, G. H., K. G. Dodds, and G. D. Bruce. 1999. Combined effect of the Inverdale and Booroola prolificacy genes on ovulation rate in sheep. Proc. 13th Conf. Assoc. Adv. Anim. Breed. and Genet. 13:74–77.
Davis, G. H., S. M. Galloway, I. K. Ross, S. M. Gregan, J. Ward, B. V. Nimbkar, P. M. Ghalsasi, C. Nimbkar, G. D. Gray, Subandriyo, I. Inounu, B. Tiesnamurti, E. Martyniuk, E. Eythorsdottir, P. Mulsant, F. Lecerf, J. P. Hanrahan, G. E. Bradford, and T. Wilson. 2002. DNA tests in prolific sheep from eight countries provide new evidence on origin of the Booroola (FecB) mutation. Biol. Reprod. 66:1869–1874.[Abstract/Free Full Text]
Davis, G. H., J. C. McEwan, P. F. Fennessy, and K. G. Dodds. 1995. Discovery of the Inverdale gene (FecX). Proc. N. Z. Soc. Anim. Prod. 55:289–290.
Davis, G. H., J. C. McEwan, P. F. Fennessy, K. G. Dodds, K. P. McNatty, and W. S. O. 1992. Infertility due to bilateral ovarian hypoplasia in sheep homozygous (FecXI FecXI) for the Inverdale prolificacy gene located on the X chromosome. Biol. Reprod. 46:636–640.[Abstract]
Galloway, S. M., K. P. McNatty, L. M. Cambridge, M. P. E. Laitinen, J. L. Juengel, T. S. Jokiranta, R. J. McLaren, K. Luiro, K. G. Dodds, G. W. Montgomery, A. E. Beattie, G. H. Davis, and O. Ritvos. 2000. Mutations in an oocyte-derived growth factor gene (BMP15) cause increased ovulation rate and infertility in a dosage-sensitive manner. Nat. Genet. 25:279–283.[CrossRef][Medline]
Guan, F., S. R. Liu, G. Q. Shi, J. T. Ai, D. G. Mao, and L. G. Yang. 2006. Polymorphism of FecB gene in nine sheep breeds or strains and its effects on litter size, lamb growth and development. Acta Genetica Sinica 33:117–124.
Hanrahan, J. P., S. M. Gregan, P. Mulsant, M. Mullen, G. H. Davis, R. Powell, and S. M. Galloway. 2004. Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol. Reprod. 70:900–909.[Abstract/Free Full Text]
Jia, C. L., N. Li, X. B. Zhao, X. P. Zhu, and Z. H. Jia. 2005. Association of single nucleotide polymorphisms in exon 6 region of BMPRIB gene with litter size traits in sheep. Asian-Aust. J. Anim. Sci. 18:1375–1378.
Juengel, J. L., N. L. Hudson, D. A. Heath, P. Smith, K. L. Reader, S. B. Lawrence, A. R. O’Connell, M. P. Laitinen, M. Cranfield, N. P. Groome, O. Ritvos, and K. P. McNatty. 2002. Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep. Biol. Reprod. 67:1777–1789.[Abstract/Free Full Text]
Liu, S. F., Y. L. Jiang, and L. X. Du. 2003. Studies of BMPR-IB and BMP15 as candidate genes for fecundity in Little Tailed Han sheep. Acta Genetica Sinica 30:755–760.
Moore, R. K., F. Otsuka, and S. Shimasaki. 2003. Molecular basis of bone morphogenetic protein-15 signaling in granulosa cells. J. Biol. Chem. 278:304–310.[Abstract/Free Full Text]
Moore, R. K., and S. Shimasaki. 2005. Molecular biology and physiological role of the oocyte factor, BMP-15. Mol. Cell. Endocrinol. 234:67–73.[CrossRef][Medline]
Mulsant, P., F. Lecerf, S. Fabre, L. Schibler, P. Monget, I. Lanneluc, C. Pisselet, J. Riquet, D. Monniaux, I. Callebaut, E. Cribiu, J. Thimonier, J. Teyssier, L. Bodin, Y. Cognie, N. Chitour, and J. M. Elsen. 2001. Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. Proc. Natl. Acad. Sci. USA 98:5104–5109.[Abstract/Free Full Text]
Otsuka, F., and S. Shimasaki. 2002a. A negative feedback system between oocyte bone morphogenetic protein 15 and granulose cell kit ligand: Its role in regulating granulose cell mitosis. Proc. Natl. Acad. Sci. USA 99:8060–8065.[Abstract/Free Full Text]
Otsuka, F., and S. Shimasaki. 2002b. A novel function of bone morphogenetic protein-15 in the pituitary:selective synthesis and secretion of FSH by gonadotropes. Endocrinology 143:4938–4941.[Abstract]
Otsuka, F., S. Yamamoto, G. F. Erickson, and S. Shimasaki. 2001. Bone morphogenetic protein-15 inhibits follicle-stimulating hormone (FSH) action by suppressing FSH receptor expression. J. Biol. Chem. 276:11387–11392.[Abstract/Free Full Text]
Otsuka, F., Z. Yao, T. Lee, S. Yamamoto, G. F. Erickson, and S. Shimasaki. 2000. Bone morphogenetic protein-15. Identification of target cells and biological functions. J. Biol. Chem. 275:39523–39528.[Abstract/Free Full Text]
Souza, C. J. H., C. MacDougall, B. K. Campbell, A. S. McNeilly, and D. T. Baird. 2001. The Booroola (FecB) phenotype is associated with a mutation in the bone morphogenetic receptor type 1B (BMPRIB) gene. J. Endocrinol. 169:R1–R6.[Abstract]
Tu, Y. R. 1989. Small Tailed Han sheep. Pages 50–52 in The Sheep and Goat Breeds in China. Shanghai Science and Technology Press, Shanghai, China.
Wang, J. Y., J. X. Li, and J. C. Wei. 1990. Selection and improvement on Small Tailed Han sheep. China Sheep and Goat Farming (1):1–3.
Wang, G. L., X. Z. Mao, G. H. Davis, Z. S. Zhao, L. J. Zhang, and Y. Q. Zeng. 2003a. DNA tests in Hu sheep and Han sheep (small tail) showed the existence of Booroola (FecB) mutation. J. Nanjing Agric. Univ. 26:104–106.
Wang, Q. G., F. G. Zhong, H. Li, X. H. Wang, S. R. Liu, and X. J. Chen. 2003b. The polymorphism of BMPR-IB gene associated with litter size in sheep. Grass-feeding Livest. (2):20–23.
Wang, Q. G., F. G. Zhong, H. Li, X. H. Wang, S. R. Liu, X. J. Chen, and S. Q. Gan. 2005. Detection on major gene on litter size in sheep. Hereditas (Beijing) 27:80–84.
Wilson, T., X. Y. Wu, J. L. Juengel, I. K. Ross, J. M. Lumsden, E. A. Lord, K. G. Dodds, G. A. Walling, J. C. McEwan, A. R. O’Connell, K. P. McNatty, and G. W. Montgomery. 2001. Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol. Reprod. 64:1225–1235.[Abstract/Free Full Text]
Yan, Y. D., M. X. Chu, Y. Q. Zeng, L. Fang, S. C. Ye, L. M. Wang, Q. K. Guo, D. Q. Han, Z. X. Zhang, X. J. Wang, and X. Z. Zhang. 2005. Study on bone morphogenetic protein receptor IB as a candidate gene for prolificacy in Small Tailed Han sheep and Hu sheep. J. Agric. Biotechnol. 13:66–71.
Top
Abstract
INTRODUCTION
