Dietmar Bächner

Abnormal myotonic dystrophy protein kinase levels produce only mild myopathy in mice.

Myotonic dystrophy (DM) is commonly associated with CTG repeat expansions within the gene for DM–protein kinase (DMPK). The effect of altered expression levels of DMPK, which is ubiquitously expressed in all muscle cell lineages during development, was examined by disrupting the endogenous Dmpk gene and overexpressing a normal human DMPK transgene in mice. Nullizygous (−/−) mice showed only inconsistent and minor size changes in head and neck muscle fibres at older age, animals with the highest DMPK transgene expression showed hypertrophic cardiomyopathy and enhanced neonatal mortality. However, both models lack other frequent DM symptoms including the fibre–type dependent atrophy, myotonia, cataract and male–infertility. These results strengthen the contention that simple loss– or gain–of–expression of DMPK is not the only crucial requirement for development of the disease.

Developmental expression analysis of murine autotaxin (ATX)

The murine homologue of the human motility-stimulating protein autotaxin (ATX) was identified as a BMP2 upregulated gene by subtractive cloning from mesenchymal progenitors C3H10T1/2 (Bächner, D., Ahrens, M., Betat, N., Schröder, D., Hoffmann. A., Lauber, J., Steinert, P., Flohe, L., Gross, G., 1998. Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2). Dev. Dyn. 213, 398-411). ATX mRNA transcription is induced during BMP2 mediated osteo-/chondrogenic differentiation in vitro several orders of magnitude. To delineate a potential role for ATX in osteo-/chondrogenic development, its expression pattern during murine embryogenesis was examined in comparison with Col1a1 and Col2a1, a marker either of osteoblast, odontoblast and tendon or of chondrocyte development, respectively. Localization of murine ATX was first observed in the floor plate of the neural tube at day 9.5 of mouse embryonic development. Later, enhanced ATX expression levels were observed in proliferating subepithelial mesenchyme, during osteo-/chondrogenic and tooth development, in choroid plexus epithelium, in late kidney development, and in smooth muscles of the ductus deferens and the bladder.

Developmental expression of the cell adhesion molecule-like protein tyrosine phosphatases LAR, RPTPδ and RPTPσ in the mouse

Abstract Using RNA in situ hybridization we compared the expression patterns of the cell adhesion molecule-like receptor-type protein tyrosine phosphatases LAR, RPTP δ and RPTP σ during mouse development. We found that LAR is expressed in basal lamina-associated epithelial tissues of (neuro)ectodermal, neural crest/ectomesenchyme and endodermal origin. RPTP σ is found in (neuro)ectodermal, neural crest-derived systems and in mesoderm-derived tissues. The expression pattern of RPTP σ largely parallels that of RPTP σ , in concordance with their proposed evolutionary history ( Schaapveld et al., 1995 ).

A comparison of the expression pattern of five genes of the family of small leucine-rich proteoglycans during mouse development.

For five members of the family of the small leucine‐rich proteoglycans (SLRPs), the expression pattern during fetal development was analyzed. RNA in situ hybridization on whole body sections of mouse embryos was performed for biglycan (Bgn), decorin (Dcn), fibromodulin (Fmod), chondroadherin (Chad), and lumican (Lum). Special attention was given to the question of whether these patterns coincide only with sites of collagen secretion in connective tissue during tissue modeling or if expression can be observed at specific sites of organ differentiation also. In general, Fmod, Lum, and Bgn are expressed at sites of cartilage and bone formation and interstitial tissue deposition; Chad is expressed only at sites of cartilage; and Dcn is expressed only at sites of interstitial tissue deposition. However, there are some distinct developmental stages where no collagen secretion is known to occur. For example, this applies for the expression of Fmod in the forming somites of stage 9.5 postconception (p.c.), for Dcn and Lum in later stage embryos in the pituitary gland and dorsal root ganglia, and for Bgn and Dcn during differentiation in the kidney. These studies provide further evidence for a role of these molecules during connective tissue organization but also for an involvement at specific sites of organ differentiation.