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U Philipp

Publications and source records attributed to U Philipp.

18 recordsLinked to original sources
PubMed2005

Chromosomal assignment of the canine melanophilin gene (MLPH): a candidate gene for coat color dilution in Pinschers.

Pinschers affected by coat color dilution show a specific pigmentation phenotype. The dilute pigmentation phenotype leads to a silver-blue appearance of the eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in Pinschers is sometimes accompanied by hair loss and a recurrent infection of the hair follicles. In human and mice, several well-characterized genes are responsible for similar pigment variations. To investigate the genetic cause of the coat color dilution in Pinschers, we isolated BAC clones containing the canine ortholog of the known murine color dilution gene Mlph. RH mapping of the canine MLPH gene was performed using an STS marker derived from BAC sequences. Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the canine MLPH gene was assigned to CFA25q24.

Animals↗
PubMed2005

Molecular cloning, expression analysis and assignment of the porcine tumor necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34-->q36 by fluorescence in situ hybridization and radiation hybrid mapping.

We have cloned the complete coding region of the porcine TNFSF10 gene. The porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85% identity with human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding sequences, respectively. The deduced porcine TNFSF10 protein consists of 289 amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of 8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when compared with human, rat and mouse sequences, respectively. Northern blot analysis detected TNFSF10-specific transcripts (approximately 1.7 kb) in various organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR studies of various organs from fetal (days 73 and 98) and postnatal stages (two weeks, eight months) demonstrated developmental and tissue-specific regulation of TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10 BAC clone has been assigned to SSC13q34-->q36. Additionally, the localization of the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel.

Amino Acid Sequence↗
PubMed1999

Amyloidogenic function of the Alzheimer's disease-associated presenilin 1 in the absence of endoproteolysis.

Alzheimer's disease (AD) is characterized by the invariant accumulation of senile plaques predominantly composed of the pathologically relevant 42-amino acid amyloid beta-peptide (Abeta42). The presenilin (PS) proteins play a key role in Abeta generation. FAD-associated mutations in PS1 and PS2 enhance the production of Abeta42, and PS1 is required for physiological Abeta production, since a gene knockout of PS1 and dominant negative mutations of PS1 abolish Abeta generation. PS proteins undergo endoproteolytic processing, and current evidence indicates that fragment formation may be required for the amyloidogenic function of PS. We have now determined the sequence requirements for endoproteolysis of PS1. Mutagenizing amino acids at the previously determined major cleavage site (amino acid 298) had no effect on PS1 endoproteolysis. In contrast, mutations or deletions at the additional cleavage site around amino acid 292 blocked endoproteolysis. The uncleavable PS1 derivatives accumulated as full-length proteins and replaced the endogenous PS1 proteins. In contrast to the previously described aspartate mutations within transmembrane domains 6 and 7, the uncleaved PS1 variants do not act as dominant negative inhibitors of Abeta production. Moreover, when a FAD-associated mutation (M146L) was combined with a mutation blocking endoproteolysis, Abeta42 production still reached pathological levels. These data therefore demonstrate that endoproteolysis of presenilins is not an absolute prerequisite for the amyloidogenic function of PS1. These data also show that accumulation of the PS1 holoprotein is not associated with the pathological activity of PS1 mutations as suggested previously.

Alzheimer Disease↗
PubMed1999

The biological and pathological function of the presenilin-1 Deltaexon 9 mutation is independent of its defect to undergo proteolytic processing.

The two homologous presenilins are key factors for the generation of amyloid beta-peptide (Abeta), since Alzheimer's disease (AD)-associated mutations enhance the production of the pathologically relevant 42-amino acid Abeta (Abeta42), and a gene knockout of presenilin-1 (PS1) significantly inhibits total Abeta production. Presenilins undergo proteolytic processing within the domain encoded by exon 9, a process that may be closely related to their biological and pathological activity. An AD-associated mutation within the PS1 gene deletes exon 9 (PS1Deltaexon9) due to a splicing error and results in the accumulation of the uncleaved full-length protein. We now demonstrate the unexpected finding that the pathological activity of PS1Deltaexon9 is independent of its lack to undergo proteolytic processing, but is rather due to a point mutation (S290C) occurring at the aberrant exon 8/10 splice junction. Mutagenizing the cysteine residue at position 290 to the original serine residue completely inhibits the pathological activity in regard to the elevated production of Abeta42. Like PS1Deltaexon9, the resulting presenilin variant (PS1Deltaexon9 C290S) accumulates as an uncleaved protein and fully replaces endogenous presenilin fragments. Moreover, PS1Deltaexon9 C290S exhibits a significantly increased biological activity in a highly sensitive in vivo assay as compared with the AD-associated mutation. Therefore not only the increased Abeta42 production but also the decreased biological function of PS1Deltaexon9 is due to a point mutation and independent of the lack of proteolytic processing.

Alzheimer Disease↗
PubMed1973

Mechanisms of central transmission of respiratory reflexes.

Several types of respiratory reflex actions can be discerned according to the reactions of typical respiratory neurons in the efferent part of the central rhythmogenic structure. Whereas respiration runs closely parallel with inspiratory neuron activity the behaviour of expiratory neurons cannot be derived from the resulting reflex changes of respiration. So expiratory apnoea can be combined with continuous activity or with inactivation of expiratory neurons. Extracellular records from a closed uniformly reacting population of expiratory neurons and from neighbouring reticular neurons allowed experimental differentiation between different types of central respiratory reflex actions. In experiments on anaesthetized dogs the responses to chemoreceptor and baroreceptor excitation and to pulmonary inflation were investigated. Chemoreceptor excitation leads to activation of inspiratory, expiratory, and reticular neurons, whereas the baroreceptor afferents act in the opposite direction. In contrast moderate lung inflation causes more specific effects: activation of expiratory neurons, inactivation of inspiratory neurons. But if a certain degree of lung inflations is exceeded a more general inhibition of both inspiratory and expiratory neurons takes place. These results only apply to the "typical" respiratory neurons. The principles used to distinguish between the different types of reflexes are proposed for a basis of classification also of other neural, chemical or pharmacological influences on breathing.

Animals↗