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Biomedical subjects

G A Friedrich

Publications and source records attributed to G A Friedrich.

8 recordsLinked to original sources
PubMed1998

Disruption and sequence identification of 2,000 genes in mouse embryonic stem cells.

The dramatic increase in sequence information in the form of expressed sequence tags (ESTs) and genomic sequence has created a 'gene function gap' with the identification of new genes far outpacing the rate at which their function can be identified. The ability to create mutations in embryonic stem (ES) cells on a large scale by tagged random mutagenesis provides a powerful approach for determining gene function in a mammalian system; this approach is well established in lower organisms. Here we describe a high-throughput mutagenesis method based on gene trapping that allows the automated identification of sequence tags from the mutated genes. This method traps and mutates genes regardless of their expression status in ES cells. To facilitate the study of gene function on a large scale, we are using these techniques to create a library of ES cells called Omnibank, from which sequence-tagged mutations in 2,000 genes are described.

Animals↗
PubMed1998

Correlation between hip joint laxity and subsequent coxarthrosis in dogs.

In a prospective study the degree of hip joint laxity was compared with subsequent hip joint development. A total of 70 non-selected adult dogs from 34 breeds presented for hip dysplasia screening was examined. The degree of hip laxity was quantitated using a newly developed radiographic stress technique. The dogs were re-examined according to the standard radiographic technique after 1 year or more. There was a positive correlation (r = 0.58) between the degree of subluxation (SI) and the subsequent Canine hip dysplasia (CHD) grade. All dogs with an SI value of up to 0.35 developed hip joints ranging between normal and mildly dysplastic at worst. Of the dogs with an SI value higher than 0.35, 76% developed hip dysplasia. Of those 40 dogs grading normal or borderline normal on standard radiographs, 15% demonstrated lax hip joints with an SI of more than 0.35. Breed-specific differences in the correlation of degree of hip joint laxity to the development of coxarthrosis were noted. If both excessive hip joint laxity and development of arthrosis are considered exclusion criteria for breeding dogs, then the current mode of selection does not adequately restrict potential breeding stock. Only dogs demonstrating an SI of 0.35 or less on stress radiographs and graded normal or borderline normal on standard radiographs should be used for breeding, equivalent to 49% of all dogs examined in this study. A further 36% of the dogs examined, most of them currently still accepted as breeding dogs, would not pass. Breed-specific acceptable degree of hip joint laxity in breeding dogs should be determined. Selecting breeding dogs based on the results of hip joint laxity assessment may further decrease the incidence of CHD in the offspring.

Animals↗
PubMed1998

Comprehensive mammalian genetics: history and future prospects of gene trapping in the mouse.

Gene trapping has matured into a tool with tremendous potential for mammalian biology. It both mutates and helps identify genes and can be streamlined so that many thousands of insertions can be characterized. In only a few years most of the genome of the mouse will be tagged and mutated using the latest gene trap designs. By creating such a resource, costly and time consuming alternative methods of mutagenesis and gene identification can be avoided allowing biologists to concentrate on determining gene function in vivo. This will mean a major shift in how the genome will be mined for new drug targets. Notably, gene discovery via gene traps does not suffer from the limitations of other methods as it is not biased by expression level. Mouse strains with specific gene mutations can be easily derived from a gene trap library constructed using embryonic stem cells. These strains will help determine the role of the gene product in mammalian physiology and hence the relevance of the gene product to human disease.

Animals↗
PubMed1997

The secretory protein Sec8 is required for paraxial mesoderm formation in the mouse.

The sec8 gene, isolated in a gene trap screen in embryonic stem cells, is required for paraxial mesoderm formation in the mouse. Homozygous sec8 mutant embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly afterward. The genomic locus and cDNA of the sec8 gene have been cloned. An open reading frame in the cDNA encodes a 971-amino-acid leucine-rich protein, similar to rat rSec8. A description of the mutant phenotype and the cloning of the gene is presented here and the results are considered in light of the possibility that the Sec8 protein is involved in secretion.

Amino Acid Sequence↗
PubMed1994

Transcriptional enhancer factor 1 disruption by a retroviral gene trap leads to heart defects and embryonic lethality in mice.

We have used a retroviral gene trap in embryonic stem (ES) cells to derive a recessive embryonic lethal mouse strain, ROSA beta-geo5. Mutant embryos display an enlarged pericardial cavity, bradycardia, a dilated fourth ventricle in the brain, and die between embryonic days 11 and 12. Whereas heart development in the mutant embryos is extensive, the ventricular wall is abnormally thin with a reduced number of trabeculae. Cloning of the trapped gene indicates that proviral insertion creates a null mutation in the transcriptional enhancer factor 1 (TEF-1) gene. Although transcription of a number of muscle-specific genes believed to be TEF-1 targets appears normal, the defect in cardiogenesis is likely attributable to diminished transcription of one or several cardiac-specific genes.

Amino Acid Sequence↗
PubMedDate not supplied

A radiographic stress technique for evaluation of coxofemoral joint laxity in dogs.

OBJECTIVE: To develop a radiographic stress technique to quantify hip joint laxity in dogs. STUDY DESIGN: Prospective study on client-owned dogs presented for hip dysplasia screening. ANIMAL POPULATION: 302 nonselected dogs (63 breeds). METHODS: Dogs were sedated and placed in dorsal recumbency. During pelvic radiography, the femoral heads were displaced manually in a craniodorsal direction. On these stress radiographs, the degree of lateral displacement of the femoral heads was assessed in terms of a subluxation index (SI) and compared with the degree of femoral head subluxation and the severity of hip dysplasia found on conventional extended hindlimb radiographs. RESULTS: The degree of subluxation on stress radiographs was significantly greater than on conventional radiographs. Correlation between the severity of canine hip dysplasia (CHD), graded according to conventional techniques, and the degree of subluxation, induced by radiographic stress technique, was positive (r = .57; P<.0001). Two critical SI values were noted. Of the dogs with an SI value of 0.3 or less, 99% were classified as CHD grade normal, borderline, or mildly dysplastic. In dogs with an SI value between 0.3 and 0.5, CHD grading ranged from normal to severely dysplastic. Of the dogs with an SI value greater than 0.5, 95% had dysplastic hip joints. CONCLUSIONS: Hip joint laxity cannot be quantified precisely on standard position radiographs. The proposed stress technique yields significantly higher degrees of femoral head subluxation than the standard position.

Animals↗