Generation of goats by nuclear transfer: a retrospective analysis of a commercial operation (1998-2010)
TRANSGENIC RESEARCH
Authors: Gavin, W.; Buzzell, N.; Blash, S.; Chen, L.; Hawkins, N.; Miner, K.; Pollock, D.; Porter, C.; Bonzo, D.; Meade, H.
Abstract
At LFB USA, Inc., the ultimate use for transgenic cloned goats is for the production of recombinant human protein therapeutics in their milk. This retrospective analysis of the Somatic Cell Nuclear Transfer (SCNT) program, spanning from 1998 to 2010, examined parameters potentially affecting the outcomes and efficiencies in this commercial operation. Over 37,000 + ova were utilized in the SCNT protocol producing a total of 203 cloned goats. Fifty one (51) clones were produced from non-transfected (transgenic and non-transgenic animal donor) cell lines and 152 clones were produced from transfected cell lines. Comparisons and summaries of (a) transfected versus non-transfected cell lines, (b) relationship of SCNT parameters to offspring produced, (c) skin versus fetal cells, (d) fresh versus cryopreserved cells, (e) parameters from all cell lines used versus those producing SCNT offspring, (f) variation among cell sources, (g) methods of SCNT parturition management and effects on live offspring, and lastly (h) SCNT variation by program are reported. Findings indicate that (a) non-transfected cell lines were more efficient versus transfected cell lines in generating viable cloned offspring on a per reconstructed embryo transferred basis, (b) transfected fetal fibroblasts had improved efficiency versus transfected skin fibroblasts, (c) the percentage of non-transfected cell lines that produced offspring was statistically higher than transfected cell lines, (d) and induction of parturition improved the percentage of viable offspring. In summary, this retrospective analysis on the SCNT process has identified certain parameters for improved efficiency in producing viable cloned goats in a commercial setting.
Effect of gestational and lactational nonylphenol exposure on airway inflammation in ovalbumin-induced asthmatic rat pups
CHEMOSPHERE
Authors: Yu, Jie; Tuo, FangXu; Luo, Ya; Xu, Jie
Abstract
To investigate the effect of gestational and lactational nonylphenol (NP) exposure on airway inflammation in ovalbumin (OVA)-induced asthmatic pups. Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 7 to postnatal day 21. The results showed that the NP content in the lung tissues of pups in the 100 mg/kg NP group was significantly higher than that of the control group (P = 0.004). In the 100 mg/kg NP group, the infiltration of lymphocytes and eosinophils with thicken smooth muscle layer and inflammatory cells in the lumen were observed in the lung tissues of pups. Osmiophilic lamellar bodies were found in the cytoplasm of type II epithelial cells; mitochondria were clearly swollen. Compared with the control group, the levels of interleukin-4 (IL-4) in BALE (P = 0.042) and ovalbumin-specific serum immunoglobulin E (OVA-sIgE) (P = 0.005) in the OVA group were significantly higher. 25 mg/kg NP-OVA co-exposure synergistically decreased nuclear factor-kappa B (NF-kappa B) mRNA expression in the lung tissues of pups; Exposure to 50 mg/kg NP combined with OVA antagonized the increased expression of high mobility group box 1 (HMGB1) mRNA in the lung tissue. The combined exposure to 50 mg/kg NP and OVA synergistically increased HMGB1 protein expression in the lung tissues. 25 mg/kg NP-OVA co-exposure antagonized the increased nuclear factor-kappa B (NF-kappa B) protein expression in the lung tissues. There was a positive correlation between NP content and HMGB1 protein expression in the lung tissue of asthmatic pups (r = 0.602, P < 0.001). In conclusion, gestational and lactational exposure to 100 mg/kg NP in maternal rats exacerbated airway inflammation in OVA-induced asthmatic pups, and there is an interactive effect between NP and OVA. When the perinatal rats were exposed to 100 mg/kg NP, the levels of HMGB1 and NF-kappa B in the lung tissues of OVA-induced asthmatic pups were increased. (C) 2020 Published by Elsevier Ltd.