C57BL/6-Tg(Thy1-env)E337Nath/J

Stock number: 028326
Product name: HERV-K env

Description

These HERV-K env transgenic mice express a neuron specific transgene containing the codon optimized human endogenous retrovirus envelope protein and develop progressive motor neuron disease.

Detailed description

These transgenic mice express the codon optimized human endogenous retrovirus envelope protein, HERV-K env, gene under the control of the neuron specific mouse Thy1, thymus cell antigen 1, theta, gene promoter. Hemizygous mice develop progressive motor impairment at 2 to 3 months of age, with half of the transgenic mice dying by 10 months of age due to muscle weakness of the limbs, spine and thoracic cage. Only the upper and lower motor neurons are involved in the progressive motor neuron pathology. Transgene expression is detected in cortical neurons (neuronal cell body cytoplasm and apical dendrites) and spinal cord by Western blot analysis and immunostaining, and in brain tissue by RT-PCR. Expression level of the HERV-K env mRNA is 2 fold higher in transgenic mice compared to postmortem brain tissue from ALS patients. HERV-K env positive neurons exhibit adjacent regions of astrocytosis and abnormal dendrite morphology including reduced dendrite length, branching, complexity, as well as fewer dendritic spines. Transgenic mice exhibit approximately 22% thinner motor cortex and have fewer Ctip2 positive corticospinal motor neurons compared to nontransgenic controls. Neurons of the motor cortex display nucleolar stress and dysfunction, and double-strand DNA breakage. Electrophysiological examination of neurons reveal abnormalities including increased input resistance and intrinsic excitability. The Donating Investigator has not attempted to make the strain homozygous.

Development

A transgenic construct containing the 2.1kb codon optimized human endogenous retrovirus envelope protein, HERV-K env, gene under the control of the neuron specific mouse Thy1, thymus cell antigen 1, theta, gene promoter, was injected into fertilized C57BL/6 mouse eggs. Founder line E337 was subsequently established. The mice were then backcrossed to C57BL/6J for approximately 3 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(Thy1-env)E337Nath
Name: transgene insertion E337, Avindra Nath
MGI accession ID: MGI:5751973
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Thy1-env)E337Nath
Marker name: transgene insertion E337, Avindra Nath
Chromosome: UN
Strain of origin: C57BL/6
Expressed genes: HERV-K env,human endogenous retrovirus envelope protein,human
Site of expression: Transgene expression is detected in cortical neurons, spinal cord, and brain.
Molecular note: The transgenic construct contains the 2.1kb codon optimized human endogenous retrovirus envelope protein, HERV-K env, gene under the control of the neuron specific mouse Thy1, thymus cell antigen 1, theta, gene promoter. Transgene expression is detected in cortical neurons (neuronal cell body cytoplasm and apical dendrites) and spinal cord by Western blot analysis and immunostaining, and in brain tissue by RT-PCR.