Lack of complementation in somatic cell hybrids between fibroblasts from patients with different forms of cystinosis
- Univ. of California, San Diego, La Jolla (USA)
Cystinosis is an autosomal recessive disease in which three clinical forms are recognized: infantile nephropathic, with renal tubular damage by 1 year of age and progressive glomerular insufficiency; intermediate, with tubular and glomerular insufficiency beginning at a later age; benign, with no kidney damage. Skin fibroblasts cultured from patients with all types of cystinosis show increased intralysosomal free (nonprotein) cystine; however, fibroblasts from heterozygotes have normal free-cystine values. To determine whether genetic complementation occurs between the different forms, somatic cell hybrids were constructed between cells from a patient with infantile nephropathic cystinosis and cells from patients with other types of cystinosis. If complementation occurred, the hybrids would be expected to have normal cystine levels. To construct hybrid cells, a universal parent cell type (TG1-neo), which was hypoxanthine/aminopterin/thymidine (HAT) sensitive and G418 resistant was constructed from an infantile nephropathic cystinosis fibroblast strain. Polyethylene glycol fusion of TG1-neo with other cells that are not HAT sensitive or G418 resistant allowed for selection of hybrid cells in a medium containing HAT and the aminoglycoside G418. As indicated by elevated cystine levels, complementation did not occur between TG1-neo and two different benign cystinosis strains, an intermediate cystinosis strain, or another nephropathic cystinosis cell strain. When a normal fibroblast strain was fused with TG1-neo, all 15 hybrid clones studied contained normal amounts of intracellular free cystine.
- OSTI ID:
- 5563952
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America; (USA), Vol. 85:10; ISSN 0027-8424
- Country of Publication:
- United States
- Language:
- English
Similar Records
Complementation of the UV-sensitive phenotype of a xeroderma pigmentosum human cell line by transfection with a cDNA clone library
Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome
Related Subjects
CYSTINE
BIOCHEMISTRY
FIBROBLASTS
HYBRIDIZATION
HEREDITARY DISEASES
ETIOLOGY
KARYOTYPE
OXIDOREDUCTASES
PATHOGENESIS
PATIENTS
SKIN
AMINO ACIDS
ANIMAL CELLS
BODY
CARBOXYLIC ACIDS
CHEMISTRY
CONNECTIVE TISSUE CELLS
DISEASES
DISULFIDES
ENZYMES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
SOMATIC CELLS
550400* - Genetics