Overexpression of liver-type phosphofructokinase (PFKL) in transgenic-PFKL mice: implication for gene dosage in trisomy 21

The human liver-type subunit of the key glycolytic enzyme, phosphofructokinase (PFKL), is encoded by a gene residing on chromosome 21. This chromosome, when triplicated, causes the phenotypic expression of Down's syndrome (trisomy 21). Increased phosphofructokinase activity, a result of gene dosage, is commonly found in erythrocytes and fibroblasts from Down's syndrome patients. We describe the construction of transgenic mice overexpressing PFKL for use as a well-defined model system, in which the effects of PFKL overexpression in various tissues, and throughout development, can be studied. Mice transgenic for a murine PFKL ‘gene cDNA’ hybrid construct were found to overexpress PFKL in a tissue-specific manner resembling that of the endogenous enzyme. Although unchanged in adult brain, PFK specific activity was found to have been almost doubled in brains of embryonic transgenic-PFKL mice, suggesting that the extra copies of the PFKL gene are expressed during the developmental period. This pattern of overexpression of PFKL in brains of transgenic-PFKL mice suggests that gene-dosage effects may be temporally separated from some of their consequences, adding an additional layer of complexity to the analysis of gene dosage in trisomy 21.

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Isolation of chromosome 21-specific sequences responsible for the phenotypic expression of Down's syndrome

Biochemical Society Transactions ◽

10.1042/bst0140476 ◽

1986 ◽

Vol 14 (2) ◽

pp. 476-477

Author(s):

L. A. J. STEFANI ◽

A. M. MILLINGTON-WARD ◽

P. PEARSON ◽

N. C. NEVIN

Keyword(s):

Down's Syndrome ◽

Phenotypic Expression ◽

Down’S Syndrome ◽

Chromosome 21 ◽

Specific Sequences

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Gene dosage of CuZnSOD and Down's syndrome: diminished prostaglandin synthesis in human trisomy 21, transfected cells and transgenic mice.

The EMBO Journal ◽

10.1002/j.1460-2075.1991.tb07745.x ◽

1991 ◽

Vol 10 (8) ◽

pp. 2119-2124 ◽

Cited By ~ 30

Author(s):

D. Minc-Golomb ◽

H. Knobler ◽

Y. Groner

Keyword(s):

Transgenic Mice ◽

Trisomy 21 ◽

Gene Dosage ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Prostaglandin Synthesis ◽

Transfected Cells

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Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down’s Syndrome and Trisomy-21 Linked Disease

Cellular and Molecular Neurobiology ◽

10.1007/s10571-017-0514-0 ◽

2017 ◽

Vol 38 (3) ◽

pp. 769-774 ◽

Cited By ~ 8

Author(s):

P. N. Alexandrov ◽

M. E. Percy ◽

Walter J. Lukiw

Keyword(s):

Trisomy 21 ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Chromosome 21

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Genetic variation in the COL6A1 region is associated with congenital heart defects in trisomy 21 (Down's syndrome)

Annals of Human Genetics ◽

10.1111/j.1469-1809.1995.tb00746.x ◽

1995 ◽

Vol 59 (3) ◽

pp. 253-269 ◽

Cited By ~ 31

Author(s):

G. E. DAVIES ◽

C. M. HOWARD ◽

M. J. FARRER ◽

M. M. COLEMAN ◽

L. B. BENNETT ◽

...

Keyword(s):

Genetic Variation ◽

Congenital Heart Defects ◽

Trisomy 21 ◽

Congenital Heart ◽

Heart Defects ◽

Down's Syndrome ◽

Down’S Syndrome

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Down's syndrome and the molecular biology of chromosome 21

Progress in Neurobiology ◽

10.1016/0301-0082(88)90033-0 ◽

1988 ◽

Vol 30 (6) ◽

pp. 507-530 ◽

Cited By ~ 21

Author(s):

David N. Cooper ◽

Christine Hall

Keyword(s):

Molecular Biology ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Chromosome 21

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Trisomy 21 in One of Twin Fetuses

PEDIATRICS ◽

10.1542/peds.62.1.52 ◽

1978 ◽

Vol 62 (1) ◽

pp. 52-53

Author(s):

Richard H. Heller ◽

Lee S. Palmer

Keyword(s):

Prenatal Diagnosis ◽

Trisomy 21 ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Healthy Infant ◽

The Other ◽

Technical Problems ◽

The Family ◽

Successful Execution

Both the detection of twins and the successful execution of a double amniocentesis pose significant technical problems in prenatal diagnosis. A case is reported in which one of twin fetuses had trisomy 21 and the other was chromosomally normal. Following counseling, the family chose to continue the pregnancy. At term, the mother was delivered of a healthy infant and a severely macerated fetus with stigmata suggestive of Down's syndrome.

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To Find out the Value of Hypermobility in Down’s Syndrome

Journal of Gynecology Research Reviews & Reports ◽

10.47363/jgrrr/2021(3)135 ◽

2021 ◽

pp. 1-4

Author(s):

Vadivelan Kanniappan ◽

Keyword(s):

Chromosomal Abnormalities ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Joint Hypermobility ◽

Chromosome 21 ◽

Knee Joints ◽

Trunk Flexion ◽

Total Point ◽

Study Setting

Background: Down syndrome, the result of trisomy of chromosome 21, is one of the most common chromosomal abnormalities. Patients have a characteristic 8 facial appearance, variable levels of intelligence and self-care skills, and a variety of associated medical conditions. Orthopaedic manifestations occur frequently; most are related to hypotonia, joint hypermobility, and ligamentous laxity. Objective: Aim of the study is to find out the value of hyper mobility in down’s syndrome. Methodology: 30 Subjects including in my study ,study duration is 4 weeks, study setting is Maithree Special School, NIEPMD, REC Centre SRM Hospital. Outcome Measures: Beighton Scale, Goniometre Results: This beighton scale consists of goniometer measurement of thumb, metacarcophalangeal joints ,elbow joint , knee joints,trunk flexion .total point (9) point.50%of sample was scored 9 point.10%of sample was scored 8 point.7%of sample was s cored 7 points.35%of sample was scored 6 points. Conclusion: This study concluded that Down’s Syndrome children has hypermobility which needs to be investigated early and treated for better quality of life.

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Cast aside

10.1093/med/9780198854807.003.0027 ◽

2021 ◽

pp. 191-196

Author(s):

Michael Obladen

Keyword(s):

Trisomy 21 ◽

Homo Sapiens ◽

Down's Syndrome ◽

Scientific Progress ◽

Down’S Syndrome ◽

Chromosomal Anomalies ◽

Additional Chromosome ◽

Ethnic Classification ◽

The Right ◽

Invasive Techniques

Trisomy 21 originated with Homo sapiens, or even before, as it exists in other primates. However, in antiquity, Down’s syndrome was rare: mothers were younger, and children failed to reach adulthood. For centuries, trisomy 21 and hypothyreosis were confused. Scientific reports originated from asylums for the mentally retarded. In 1866, John Langdon Down at Earlswood published a description of symptoms in his ‘Ethnic classification of idiots’ and coined the term ‘Mongolian’. Jerôme Lejeune identified an additional chromosome 21 causing the disorder. Maternal age rose markedly for various reasons, as did the prevalence of trisomy 21. From 1968, high-risk pregnancies were screened and interrupted because of Down’s syndrome. Non-invasive techniques now enable all pregnancies to be screened to detect chromosomal anomalies early and precisely. The topic is hotly debated and consensus unlikely. Legislation will not halt scientific progress, but it should ensure that in the same society contradictory attitudes can be held and mutually respected: the right to accept a disabled infant and the right not to accept it.

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