RESUMO
The Jining Grey is a prolific local goat breed in P.R. China. Bone morphogenetic protein 15 (BMP15) gene that controls high fecundity of Inverdale, Hanna, Lacaune, Belclare, Cambridge, and Small Tailed Han ewes was studied as a candidate gene for the prolificacy of Jining Grey goats. According to the sequence of ovine BMP15 gene, six pairs of primers were designed to detect single nucleotide polymorphisms in exon 1 and exon 2 of the BMP15 gene in both high fecundity breed (Jining Grey goats) and low fecundity breeds (Boer, Liaoning Cashmere, and Inner Mongolia Cashmere goats) by single strand conformation polymorphism (SSCP). Two pairs of primers (F1/R1 and F2/R2) were used to amplify the exon 1. Four pairs of primers (F3/R3, F4/R4, F5/R5, and F6/R6) were used to amplify the exon 2. Only the products amplified by primer F5/R5 displayed polymorphism. Results indicated that two genotypes (AA and AB) were detected in prolific Jining Grey goats and only one genotype (AA) was detected in low fecundity goat breeds. In Jining Grey goats frequencies of genotypes AA and AB were 0.10 and 0.90, respectively. Sequencing revealed two point mutations (G963A and G1050C) of BMP15 gene in the AB genotype in comparison to the AA genotype. In Jining Grey goats the heterozygous AB does had 1.13 (p < 0.01) kids more than the homozygous AA does. These results preliminarily showed that the BMP15 gene is either a major gene that influences the prolificacy of Jining Grey goats or a molecular genetic marker in close linkage with such a gene.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Fertilidade/genética , Cabras/genética , Animais , DNA/química , DNA/genética , Eletroforese em Gel de Poliacrilamida , Feminino , Genótipo , Análise dos Mínimos Quadrados , Tamanho da Ninhada de Vivíparos/genética , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Nucleotídeo Único , Gravidez , Análise de Sequência de DNARESUMO
Fibroblast growth factor receptor-1 (FGFR-1) has been used as a target for anti-angiogeneic therapy of cancer. The strategies of combining anti-angiogenic biotherapy with chemotherapeutic drugs show potential and promise for cancer therapy. In this study, we evaluated the anti-tumour efficacy of chicken FGFR-1 (cFR-1) vaccine combined with low-dose gemcitabine in two mice tumour models. We found that both the cFR-1 vaccine and low-dose gemcitabine can suppress tumour growth to some extent. Remarkably, the combination strategy produces an apparent decrease in tumour volume, microvessel density and tumour cell proliferation, and an increase of apoptosis without obvious side-effects compared with either therapy alone. Moreover, the combination strategy also demonstrated synergistic indices against tumour growth and angiogenesis. Furthermore, auto-antibodies against mouse FGFR-1 were identified. These findings support the idea that the combination strategy synergistically strengthens anti-tumour activity via suppression of tumour angiogenesis without overt toxicity in tumour-bearing mice.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Animais , Autoimunidade , Vacinas Anticâncer/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Sinergismo Farmacológico , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/administração & dosagem , Proteínas Recombinantes/administração & dosagem , GencitabinaRESUMO
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 FecB(B)/FecB(B) and FecB(B)/FecB(+) had 1.40 (P < 0.01) and 1.11 (P < 0.01) more lambs, respectively, than those with genotype FecB(+)/FecB(+). The same FecX(G) 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 FecX(G)/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.