My Publications (4)
1: Genetic dependence of central corneal thickness among inbred strains of mice.
Investigative Ophthalmology & Visual Science 51 160-171 2010
Lively GD, Jiang B, Hedberg-Buenz A, Chang B, Petersen GE, Wang K, Kuehn MH, Anderson MG.
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PURPOSE: Central corneal thickness (CCT) exhibits broad variability. For unknown reasons, CCT also associates with diseases not typically considered corneal, particularly glaucoma. The purpose of this study was to test the strain dependence of CCT variability among inbred mice and identify cellular and molecular factors associated with differing CCT. METHODS: Methodology for measuring murine CCT with ultrasound pachymetry was developed and used to measure CCT among 17 strains of mice. Corneas from three strains with nonoverlapping differences in CCT (C57BLKS/J, C57BL/6J, and SJL/J) were compared by histology, transmission electron microscopy, and expression profiling with gene microarrays. RESULTS: CCT in mice was highly strain dependent. CCT exhibited continuous variation from 89.2 microm in C57BLKS/J to 123.8 microm in SJL/J. Stromal thickness was the major determinant of the varying murine CCT, with epithelial thickness also contributing. Corneal expression levels of many genes differed between strains with differing CCT, but most of these changes did not correlate with the changes observed in previously studied corneal diseases nor did they correlate with genes encoding major structural proteins of the cornea. CONCLUSIONS: Murine CCT has been measured with a variety of different techniques, but only among a limited number of different strains. Here, pachymetry was established as an additional tool and used to conduct a broad survey of different strains of inbred mice. These results demonstrated that murine CCT was highly influenced by genetic background and established a baseline for future genetic approaches to further elucidate mechanisms regulating CCT and its disease associations.
2: Lyst mutation in mice recapitulates iris defects of human exfoliation syndrome.
Investigative Ophthalmology & Visual Science 50 1205-1214 2009
Trantow CM, Mao M, Petersen GE, Alward EM, Alward WL, Fingert JH, Anderson MG.
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PURPOSE: Human eyes with exfoliation syndrome (XFS) exhibit a distinctive pattern of iris transillumination defects that are recapitulated in Lyst mutant mice carrying the beige allele. The purpose of this study was to determine the anatomic basis for Lyst-mediated transillumination defects, test whether Lyst mutant mice develop other features of XFS, and describe the molecular basis of the beige mutation. METHODS: Lyst mutant mice and strain-matched controls were compared by clinical, histologic, immunohistochemical, and molecular genetic analyses. RESULTS: Slit-lamp examination showed that Lyst mutant mice uniformly exhibit XFS-like transillumination defects. Histologic analysis showed that these defects correlate with a sawtooth morphology of the iris pigment epithelium. Lyst mutant mice also produce an exfoliative-like material and exhibit pronounced pigment dispersion. Despite these insults, Lyst mutation does not cause increased intraocular pressure or optic nerve damage in the C57BL/6J genetic background. Sequence analysis identified that the beige mutation is predicted to delete a single isoleucine from the WD40 domain of the LYST protein, suggesting that this mutation is likely to disrupt a protein-protein interaction. CONCLUSIONS: Lyst mutant eyes exhibit multiple features of XFS. Recent human genetic association studies have identified changes occurring in the LOXL1 gene as an important risk factor for XFS but also indicated that other factors contributing to risk likely exist. These results demonstrated that mutation of the Lyst gene can produce ocular features of human XFS and suggested that LYST or LYST-interacting genes may contribute to XFS.
3: Scanning transmission X-ray microscopic analysis of purified melanosomes of the mouse iris.
Micron 7 689-698 2006
Anderson MG, Haraszti T, Petersen GE, Wirick S, Jacobsen C, John SW, Grunze M.
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Melanosomes are specialized intracellular membrane bound organelles that produce and store melanin pigment. The composition of melanin and distribution of melanosomes determine the color of many mammalian tissues, including the hair, skin, and iris. However, the presence of melanosomes within a tissue carries potentially detrimental risks related to the cytotoxic indole-quinone intermediates produced during melanin synthesis. In order to study melanosomal molecules, including melanin and melanin-related intermediates, we have refined methods allowing spectromicroscopic analysis of purified melanosomes using scanning transmission X-ray microscopy. Here, we present for the first time absorption data for melanosomes at the carbon absorption edge ranging from 284 to 290 eV. High-resolution images of melanosomes at discrete energies demonstrate that fully melanized mature melanosomes are internally non-homogeneous, suggesting the presence of an organized internal sub-structure. Spectra of purified melanosomes are complex, partially described by a predominating absorption band at 288.4 eV with additional contributions from several minor bands. Differences in these spectra were detectable between samples from two strains of inbred mice known to harbor genetically determined melanosomal differences, DBA/2J and C57BL/6J, and are likely to represent signatures arising from biologically relevant and tractable phenomena.
4: A Drosophila male accessory gland protein that is a member of the serpin superfamily of proteinase inhibitors is transferred to females during mating.
Insect biochemistry and molecular biology 25 203-207 1995
Coleman S, Drähn B, Petersen G, Stolorov J, Kraus K.
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Accessory gland peptide 76A, (Acp76A), belongs to the serpin superfamily of proteins (serine protease inhibitors). Acp76A is a secreted protein synthesized only in the Drosophila melanogaster adult male accessory gland. Accumulation of the protein in males is first detected with polyclonal antibodies at 1 day after eclosion. The level of the protein in virgin males reaches a peak 5-8 days post-eclosion, and remains constant for at least 20 days. Upon mating the amount of Acp76A in males drops dramatically, but recovers by 24 h after mating. Immediately after mating the Acp76A is found in the female uterus. By 6 h after mating the amount of Acp76A detected in females is drastically reduced.
