Biomedical subjects

T S Musci

Publications and source records attributed to T S Musci.

5 recordsLinked to original sources

PubMed1997

Trapping genes expressed in the developing mouse inner ear.

Identification of the genes involved in the development of the mouse inner ear and developmental studies of mice that bear mutations in these genes is an important approach to understanding genetically determined human auditory dysfunction. Towards this end, we initiated a gene trap screen designed to simultaneously mark and mutate genes in mouse embryonic stem cells by the insertion of a lacZ reporter gene. Expression of beta-galactosidase in gene trap cell lines was monitored both before and after the addition of factors that are known to affect inner ear development. Gene trap cell lines that expressed beta-galactosidase under one or more culture conditions were used to create chimeric mouse embryos for studies of reporter gene expression in vivo. A high proportion of these gene trap insertions were expressed in the developing inner ear, suggesting that this strategy provides an effective means of identifying genes that may be involved in inner ear development or function.

Animals↗

PubMed1992

Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6.

Gene targeting in mouse embryo-derived stem cells has been used to generate mice with a disruption in the homeobox gene Hox-1.6. Mice heterozygous at the Hox-1.6 locus appear normal, whereas Hox-1.6-/Hox-1.6- mice die at or shortly after birth. These homozygotes exhibit profound defects in the formation of the external, middle and inner ears as well as in specific hindbrain nuclei, and in cranial nerves and ganglia. The affected tissues lie within a narrow region along the anteroposterior axis of the mouse but are of diverse embryonic origin. The set of defects associated with the disruption of Hox-1.6 is distinct from and nonoverlapping with that of the closely linked Hox-1.5 gene. But both mutations cause loss, rather than homeotic transformation, of tissues and structures.

Animals↗

PubMed1992

Cell mixing in the spinal cords of mouse chimeras.

With the aim of determining whether there is significant cell mixing during development of the spinal cord, experimental chimeric mice containing two genetically distinct cell populations were produced by aggregating BALB/c or BALB/c x LPT hybrid embryos with C3H/HeN embryos. The BALB/c and LPT hybrid spinal cord cells were distinguished histochemically from the C3H/HeN spinal cord cells by using beta-glucuronidase as an independent cell genotype marker. BALB/c and LPT hybrid cells have high levels of beta-glucuronidase activity, while the C3H/HeN cells have low levels. The spinal cords of the chimeras were dissected out regionally (i.e., cervical, thoracic, and lumbar areas) and were sectioned serially. Each region was then analyzed by scoring large- and medium-sized neuronal cell bodies (greater than or equal to 10 microns) whose genotypes were distinguished by their beta-glucuronidase levels. Observations of seven chimeric mice, with coat colors that varied from one extreme (5% albino) to the other (90% albino), suggest that each chimeric spinal cord is a relatively homogeneous population throughout its length. On average only 4 to 5 percentage point differences were observed when comparing left-right, cranial-caudal, and dorsal-ventral regions within a given chimera. The cell mixing, however, is not total, and regional variations were noted. Maximum left-right differences between different spinal cord levels never exceeded 18 percentage points, while in the entire cord the maximum left-right difference was 11 percentage points. When considering dorsal-ventral differences, 18 and 15 percentage points were observed within the spinal cord levels and the entire cord, respectively. However, when comparisons were made between smaller subregions (e.g., right-dorsal-cervical vs left-ventral-lumbar), larger differences of up to 30 percentage points were observed. In addition, the genotype proportions in the spinal cord were closely correlated with the visually estimated proportions of coat color genotypes.

Animals↗

PubMed1991

Swaying is a mutant allele of the proto-oncogene Wnt-1.

Mice homozygous for the recessive mutation swaying (sw) are characterized by ataxia and hypertonia, attributed to the malformation of anterior regions of the cerebellum. We show that sw is a deletion of a single base pair from the proto-oncogene Wnt-1. The deletion is predicted to cause premature termination of translation, eliminating the carboxy-terminal half of the Wnt-1 protein. Histological examination shows that sw is phenotypically identical to a previously described wnt-1 mutation introduced into mice by gene targeting. Although both mutations in Wnt-1 disrupt primarily the development of the anterior cerebellum, they also exhibit a variability in expressivity such that rostrally adjacent structures in the midbrain and caudally adjacent structures in the posterior cerebellum can also be affected.

Alleles↗

PubMed1990

All-or-none craniorachischisis in Loop-tail mutant mouse chimeras.

Mouse embryos homozygous for the mutant gene Loop-tail (Lp) are characterized by craniorachischisis, an open neural tube extending from the midbrain to the tail. In the present study, experimental chimeric mice containing mixtures of genetically mutant (from Lp/+ x Lp/+ matings) and genetically normal cells were produced. Our aim was to determine whether a 'rescue,' phenotypic gradient, or intermediate expression (i.e. alternating areas of open and closed neural tube) would be observed in these chimeras. We report our analyses of Loop-tail mutant chimeras (n = 82) by gross examination, progeny testing and quantitative analysis of glucose phosphate isomerase (GPI) isozyme levels. An all-or-none craniorachischisis in Loop-tail mutant chimeras was observed. Two multicolored adult chimeras, without any gross evidence of a neural tube defect, were shown to be homozygous Loop-tail chimeras (Lp/Lp in equilibrium +/+) by progeny testing. These results indicate that the normal phenotype can be expressed in the presence of mutant cells. Conversely, six neonates with craniorachischisis were shown to be chimeras by GPI analyses. These results show that the full mutant phenotype can be expressed even when one-third to one-half of the cells are genotypically wild-type. This study did not determine which tissue is primarily responsible for the defective neurulation in this mutant, but suggests that a 'threshold' mechanism underlies the Loop-tail mutant phenotype. In some chimeras that threshold is not reached and the neural tube remains open, whereas in other chimeras the threshold is reached and the neural tube closes completely.

Animals↗