The present study defines the organization of the mouse serum amyloid A (Saa) gene cluster on chromosome 7. A polymerase chain reaction (PCR)-based strategy was used successfully to generate a complete map of the mouse Saa genes, defining a linkage group of 3'-Saa2-5'/5'-Saa1-3'/5'-Saa4-3'/5'-Saa5-3'/5'-+ ++Saa3-3', with a maximum size of 45 kilobases (kb). This contrasts with the 150 kb human SAA gene cluster, which has been previously defined. The tight linkage of both mouse Saas and human SAAs is of potential functional significance, since the genes that encode the acute phase serum amyloid A proteins are known to exhibit co-ordinate transcriptional regulation. The present results thus suggest that selective pressure may exist which maintains the co-ordinately transcribed Saa genes in close physical proximity. This study, furthermore, demonstrates the utility of a novel PCR-based approach for fine mapping of tightly clustered linkage groups. The strategy used possesses a number of advantages over previously described techniques, such as long-range restriction mapping, since it facilitates the concurrent determination of not only precise relative map positions, but also the relative transcriptional orientations of assayed paired loci. Although presently limited in resolution to genes not more than 27 kb apart, future technical advances are likely to extend the applicability of this approach in mapping experiments to less tightly linked clusters of genes.
There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5–64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0–7.3 kPa: 45.0–54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. Impact There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5–7 kPa was inferred following systematic review.
The present study defines the organization of the mouse serum amyloid A (Saa) gene cluster on chromosome 7. A polymerase chain reaction (PCR)-based strategy was used successfully to generate a complete map of the mouse Saa genes, defining a linkage group of 3'-Saa2-5'/5'-Saa1-3'/5'-Saa4-3'/5'-Saa5-3'/5'-+ ++Saa3-3', with a maximum size of 45 kilobases (kb). This contrasts with the 150 kb human SAA gene cluster, which has been previously defined. The tight linkage of both mouse Saas and human SAAs is of potential functional significance, since the genes that encode the acute phase serum amyloid A proteins are known to exhibit co-ordinate transcriptional regulation. The present results thus suggest that selective pressure may exist which maintains the co-ordinately transcribed Saa genes in close physical proximity. This study, furthermore, demonstrates the utility of a novel PCR-based approach for fine mapping of tightly clustered linkage groups. The strategy used possesses a number of advantages over previously described techniques, such as long-range restriction mapping, since it facilitates the concurrent determination of not only precise relative map positions, but also the relative transcriptional orientations of assayed paired loci. Although presently limited in resolution to genes not more than 27 kb apart, future technical advances are likely to extend the applicability of this approach in mapping experiments to less tightly linked clusters of genes.
We have tested the hypothesis that structural allelic variants of serum amyloid A confer relative resistance to secondary amyloidosis in the A/J mouse. F2 mice, previously generated from amyloid-resistant (A/J) and amyloid-susceptible (C57BL/6J) strains and categorized with respect to amyloid susceptibility, were genotyped by polymerase chain reaction (PCR) amplification of the polymorphic D7Nds5 microsatellite. This microsatellite is closely linked to the SAA gene cluster and can discriminate between D7Nds5 alleles of A/J and C57BL/6J origin. The distribution of D7Nds5 genotypes in relation to splenic amyloid load did not deviate significantly from that expected of a random distribution, indicating that A/J amyloid resistance is not determined by variants at, or close to, D7Nds5. Therefore, structural alleles in the tightly-linked SAA gene cluster do not confer amyloid resistance in this mouse model.
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