ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
批准号:
3860872
负责人:
H ARNHEITER
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
关键词:
bacteriophage lambda congenital skeletal disorder developmental genetics evoked potentials gene expression gene mutation genetic library genetic mapping genetically modified animals hearing disorders laboratory mouse microphthalmos molecular cloning nucleic acid probes nucleic acid sequence pigmentation disorders spina bifida syndrome transfection virus genetics virus infection mechanism
中文摘要
在小鼠基因组中插入转基因有时会导致
英文摘要
Insertion of transgenes into the mouse genome occasionally results in
disruption of important endogenous genes. When bred to transgene
homozygosity, such transgenic mice may exhibit mutant phenotypes
resulting from improper functioning of the endogenous gene. We have
encountered two different insertional mutants exhibiting developmental
abnormalities. One line of mice (line 2627) harbors approximately 15
copies of a transgene on chromosome 11. The phenotype of this line is
characterized by hemivertebrae, vertebrogenic spina bifida occculta,
fusions of vertebral bodies, and short, kinky tails. This phenotype is
reminiscent of undulated, a mutation in the paired-box of the Paxl
protein encoded by the paxl gene on chromosome 2. Since Paxl and the gene
with the transgene insertion map to different chromosomes, yet produce
similar phenotypes when mutated, it is possible that the two gene
products act along the same metabolic pathway. To clone the endogenous
gene on chromosome 11, we have prepared genomic libraries in lambda phage
and are currently screening them for the presence of DNA sequences
flanking the transgene.
A second line of transgenic mice (VGA 9) harbors approximately 50 copies
of a transgene on chromosome 6. Homozygous transgenics show a complete
loss of skin, complete or near-complete loss of eve pigmentation,
microphthalmia, and a severe hearing deficiency of at least 50 dB as
analyzed by brain stem auditory evoked potential measurements done in
collaboration with Dr. Kenneth Grundfast from the LMO, NIDCD. The
hearing deficiency may be the consequence of an underdevelopment of the
stria vascularis of the cochlea where the intermediate cell layer with
its melanin-producing cells is missing. Thus, the insertion affects,
among other cell lineages, the proper development of the neural crest--
derived pigment cells. It is allelic with, and phenotypically similar
to, the mutation mi (not cloned), and shares features with two other well
characterized mutations, W (a mutation in the receptor kinase c-kit), and
S/ (a mutation in the growth factor steel). The overlap of phenotypes
suggests that these three mutations and the VGA 9 insertion affect genes
of the same metabolic pathway, Of particular interest is the connection
between VGA 9 and the human Waardenburg syndrome, a syndrome
characterized by hereditary deafness and pigment abnormalities.
Identifying the gene affected in the transgenics may provide molecular
probes useful to characterize patients with this syndrome, and may help
to understand the pathogenesis of this disease.
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ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:3846263
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:3782380
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
BIOLOGY OF MAMMALIAN HOMEODOMAIN PROTEINS
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批准号:3881759
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:6163042
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
EXPRESSION OF VIRAL PROTEINS IN TRANSGENIC MICE
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批准号:3881816
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:5203946
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MECHANISMS OF VIRAL PATHOGENESIS
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批准号:3945326
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRAL DEVELOPMENT
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批准号:6163105
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MECHANISMS OF VIRAL PATHOGENESIS
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批准号:3846241
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:2579580
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MECHANISMS OF VIRAL PATHOGENESIS
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批准号:3922622
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRA DEVELOPMENT
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批准号:5203145
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
BIOLOGY OF MAMMALIAN HOMEODOMAIN PROTEINS
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批准号:3846225
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MECHANISMS OF VIRAL PATHOGENESIS
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批准号:3860847
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项目类别:
-
资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRA DEVELOPMENT
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批准号:2579674
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MESODERMAL HOMEODOMAIN PROTEIN DURING VERTEBRAL DEVELOPMENT
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批准号:6111930
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
ANALYSIS OF INSERTIONAL MUTATIONS IN TRANSGENIC MICE
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批准号:3760289
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位:
MECHANISMS OF VIRAL PATHOGENESIS
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批准号:3881783
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:H ARNHEITER
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依托单位: