BMPR-IB Gene Research Articles

Differential expression of mRNAs encoding BMP/Smad pathway molecules in antral follicles of high- and low-fecundity Hu sheep

The Hu sheep is world-famous for its hyper-prolificacy and the bone morphogenetic protein (BMP)/Smad pathway and several other closely related molecules (GDF9, TGF-βRI) have been shown to have a close relationship with reproduction in sheep. In order to investigate the mechanism of high fecundity in Hu sheep and its relationship with the BMP/Smad pathway, 147 Hu sheep were blood sampled for detection of the FecB mutation (A746G) in the BMPRIB gene by PCR-SSCP, and sixteen adult Hu ewes classified as either high-fecundity (HF) or low-fecundity (LF) animals were sacrificed for tissue and antral follicle sampling. The tissue distribution patterns of mRNAs encoding BMP/Smad pathway molecules including BMPs (BMP2, BMP4, BMP6, BMP7 and BMP15), BMP receptors (BMPRIA, BMPRIB and BMPRII), intracellular transducers (Smad1, Smad5 and Smad4) and closely related molecules (GDF9 and TGF-βRI) were detected by RT-PCR and the gene expression levels in antral follicles were investigated by real-time PCR. The results showed that all experimental animals were homozygous for the BMPRIB (A746G) mutation, and all detected genes related to the BMP/Smad pathway and GDF9 and TGF-βRI were expressed in the ovary. In addition, BMP4, BMPRIB, BMPRII, Smad4, GDF9 and TGF-βRI mRNAs were more abundant in the antral follicles of HF animals than those of LF animals ( P < 0.05), but BMP15 mRNA was less abundant ( P < 0.01). This suggests that there could be an unidentified genetic mutation in BMPRIB, or other unidentified genes and unknown factors, which controls ovarian number by changing the expression patterns of genes known to regulate ovulation rate via the BMP/Smad pathway and closely related molecules (GDF9 and TGF-βRI).

Polymorphic and linkage analysis of microsatellite &lt;I&gt;BMS2508&lt;/I&gt; and &lt;I&gt;FecB&lt;/I&gt; gene in sheep

Genetic polymorphisms of microsatellite locus BMS2508, which was closely linked to the ovine fecundity gene FecB, were detected in prolific (Small Tail Han sheep) and non-prolific breeds of sheep (Texel, Dorset and Chinese Merino). The linkage disequilibrium between microsatellite locus BMS2508 and FecB gene of Small Tail Han sheep was also analyzed. There was the same mutation (A746G) of BMPR-IB gene in Small Tail Han sheep as that of FecB in Booroola Merino ewes, but the FecB mutation was absent in Texel, Dorset and Chinese Merino sheep. The genotype frequencies of BB, B+ and ++ were 0.485, 0.398 and 0.117 in Small Tail Han sheep, respectively. There were eight alleles varied from 94 bp to 116 bp and 15 genotypes detected at BMS2508 locus in four sheep breeds totally 438 individual. The preponderant allele was 100 bp, 94 bp, 94 bp, 112 bp, 100 bp, 100 bp, 112 bp, and the frequency was 0.453, 0.544, 0.802, 0.475, 0.483, 0.439, 0.389 in Small Tail Han (n=307), Texel (n=45), Dorset (n=46), Chinese Merino (n=40), and BB group (n=149), B+ group (n=122), ++ group (n=36) from Small Tail Han, respectively. In Small Tail Han sheep, linkage analysis indicated that there was certain linkage disequilibrium between 100 bp allele of microsatellite BMS2508 and B allele of FecB gene (D' =0.408), and certain linkage disequilibrium between 110 bp and 114 bp alleles of microsatellite BMS2508 and + allele of FecB gene (D'=0.513).

Determination of BMP-15, BMPR-1B and GDF-9 Gene Mutations of the Indigenous Sheep Breeds in Turkey

Summary The high ovulation rate and fertility are very important production traits in sheep production. The aim of the study was to determine the BMP-15, BMPR-1B and GDF-9 gene mutations which are related with the high ovulation with high ovulation rate in Chios, Kivircik, Awassi and Imrose sheep breeds. Fifty sheep from each breed were provided for this study. Blood samples for all the animals were collected in sterile-2 ml tubes containing EDTA. Genomic DNAs were isolated using a standard salt-out method. Thereafter target sites were amplified with polymerase chain reaction (PCR). FecX I , FecX H , FecX G , FecX B mutations in BMP-15 gene, FecB mutation in BMPR-IB gene and FecGH mutation in GDF-9 gene were determined by restriction fragment length polymorphism (RFLP) method. All individuals were non-carriers for these mutations, except FecX G mutation in BMP-15 gene. The animals analyzed in this study were found to be heterozygous carriers for FecX G mutation. There may be other genes affecting fertility in Anatolian breeds. For the genetically explanation of multiple lambing, especially in Chios sheep, it was concluded that different genes should be investigated in the further studies.

Türkiye’de Yetiştirilen Altı Yerli Koyun Irkında BMPR-IB (Booroola) Geninde FecB Allel Varlığının PCR-RFLP Yöntemiyle Araştırılması

Türkiye’de Yetiştirilen Altı Yerli Koyun Irkında BMPR-IB (Booroola) Geninde FecB Allel Varlığının PCR-RFLP Yöntemiyle Araştırılması

Associations of Single Nucleotide Polymorphisms in BMPR-IB Gene with Egg Production in a Synthetic Broiler Line

Egg production traits are economically important both for egg-laying and broiler lines of chicken. In sheep, the Q249R mutation in BMPR-IB is associated with ovulation rate. The present study cloned a partial chicken BMPR-IB fragment which contained the corresponding ovine Q249R mutation, including partial exon 6 and exon 7 and full-length intron 6. Five nucleotide changes were identified by alignment of the fragment amplified from Jining Bairi and Zang chickens. Among these nucleotide substitutions, the C/T transition at the base position of 35 and the A/G transition at the base position of 287 were found to be highly polymorphic, and named as SNPs C35T and A287G, respectively. For the SNP C35T, 331 hens of a synthetic broiler line were genotyped by a PCR-SSCP approach and allele C was found to be dominant. For the SNP A287G, 604 birds from the synthetic broiler line, a commercial egg-laying line, as well as three Chinese indigenous chicken breeds were genotyped by a PCR-RFLP technique. The associations of these two SNPs with egg production traits in the broiler line were analyzed. The results indicated that both the C35T and the A287G SNPs were not associated with egg production at 33wks and from 33wks to 42 wks (p>0.1), whereas the SNP A287G was associated with egg production from 47 to 56 wks (p<0.05). The dominance genetic effects on this latter trait and on egg production from 33 to 42 wks were significant (p<0.05).

Molecular mechanisms of FGF-2 inhibitory activity in the osteogenic context of mouse adipose-derived stem cells (mASCs)

Adipose-derived adult stem cells (ASCs), like their bone-marrow derived counterparts, possess the ability to differentiate down osteogenic, chondrogenic, adipogenic, and myogenic pathways. For bone differentiation of mouse ASCs (mASCs), retinoic-acid mediated upregulation of BMPR-IB has been found to be necessary. Interestingly, our previous work has also shown Fibroblast Growth Factor-2 (FGF-2) to strongly inhibit this osteogenic differentiation, even in the presence of retinoic acid. In this report, we investigated the molecular mechanisms underlying FGF-2 mediated osteogenic inhibition, demonstrating that addition of exogenous FGF-2 to mASCs antagonizes upregulation of BMPR-IB gene expression in response to retinoic acid. In addition, constitutive expression of BMPR-IB, but not BMPR-IA or BMPR-II, was found to counteract the inhibitory effects of FGF-2. Finally, p53 −/− mASCs and human ASCs, both of which express high levels of endogenous BMPR-IB, underwent normal osteogenic differentiation even in the presence of FGF-2. Collectively, our data therefore indicate that FGF-2 antagonizes the response of mASCs to retinoic acid and also suggest that threshold levels of BMPR-IB may play a crucial role both in counteracting the inhibitory role of FGF-2 and in promoting osteogenic differentiation of ASCs in the absence of retinoic acid. Moreover, the present study also indicates that differences exist between mouse and human ASCs in relationship to FGF-2 activity in the osteogenic context.

None of polymorphism of ovine fecundity major genes FecB and FecX was tested in goat

The polymorphism of mutation Q249R in BMPR-IB gene ( FecB) and loci FecX I , FecX H , FecX G , FecX B in BMP15 gene was analyzed by forced PCR-RFLP method in 550 individuals from 6 flocks or breeds of goats with litter size varied from 1.4 to 2.7 including Boer (209), Haimen (128), second generation of Boer goat crossed with Huanghuai goat (82), Huanghuai (71), Nubi (37) and Matou (23) goat. None of mutations was detected in these goat breeds and their crossbreed. These results suggest that fecundity of goat is not linked to the same loci in BMPR-IB and BMP15 as sheep. Therefore, it is necessary to seek for other genes or loci in order to develop marker assistance selection techniques and study the prolific mechanism of the goat.

The preparation of oligonucleotide chips for detecting BMPR-IB gene polymorphism in sheep

BMPR-IB gene increases ovulation rate and litter size as a major gene in Chinese Merino, because of 746 A to G mutation. The aim of this study was to make oligonucleotide chips to determine single nucleotide polymorphism (SNP) in BMPR-IB gene. The oligonucleotide chips were manufactured by using six sequence-specific oligonucleotide probes derived from polymorphic regions in the mutation and spotting the probes by microarrayer onto the aldehyde modified glass slides. The 746 A to G mutation was detected with ovine blood in reaction cells of chips. The results were identified by designed the Arraydoctor 2.0 software, in accordance with those of restriction fragment length polymorphisms (RFLP). The results showed the oligonucleotide chips are a parallel, accurate and effective way for screening prolificacy in molecular-assisted selection(MAS)of sheep.

Association of Single Nucleotide Polymorphisms in Exon 6 Region of BMPRIB Gene with Litter Size Traits in Sheep

The objective of this study was to investigate polymorphisms of BMPRIB (bone morphogenetic protein type IB receptor) gene and its effect on litter size traits in sheep. Three populations including 101 Small Tailed Han sheep, 79 Poll Dorset and 81 hybrids (Poll DorsetxSmall Tailed Han sheep) were used to detect the polymorphisms in exon 6 region of sheep BMPRIB gene. A fragment of approximately 190bp was amplified by one pair of primers, the polymorphism was revealed from the analysis of three populations by the technique of PCR -SSCP, and a mutation from A to G at 746 of the coding region was confirmed by sequencing in several individual. Statistical results indicated the distribution of allele B (with a A→G mutation) and A (without mutation) or genotype AA, AB and BB frequencies differed in three populations. BB genotype (44.55%) and B allele (66.34%) frequencies of Small Tailed Han sheep were higher than those of the others. Analysis of variance showed that the polymorphism of BMPRIB gene was associated with positive effect on litter size traits. The means of genotype BB and AB were about 1.04 and 0.74 more than genotype AA for litter size (p<0.05). Analysis of BMPRIB genotype effects on litter size in three populations indicates the existence of genotype BB or B allele increases the litter size. It suggested that the polymorphism in exon 6 (at 746 in the coding region) of sheep BMPRIB gene may be used as a marker for early selection of prolificacy in sheep.

BMP receptor 1b is required for axon guidance and cell survival in the developing retina

Previous work has documented the importance of BMPs in eye development. Loss-of-function studies in mice, with targeted deletions in either the Bmp7 or Bmp4 genes, have shown that these molecules are critical for early eye development. On the basis of the asymmetry in the dorsal–ventral expression patterns of several members of this family, it has been proposed that these molecules are critical for some aspect of dorsal–ventral patterning in the eye; however, it has been difficult to test this hypothesis because of the early requirement for BMPs in eye development. We have therefore examined the effects of loss of one of the BMP receptors, the BmprIb, on the development of the eye by using targeted deletion. We have found that BmprIb is expressed exclusively in the ventral retina during embryonic development and is required for normal ventral ganglion cell axon targeting to the optic nerve head. In mice with a targeted deletion of the BmprIb gene, many axons arising from the ventrally located ganglion cells fail to enter the optic nerve head, and instead, make abrupt turns in this region. A second phenotype in these mice is a significantly elevated inner retinal apoptosis during a distinct phase of postnatal development, at the end of neurogenesis. Our results therefore show two distinct requirements for BmprIb in mammalian retinal development.