B6.Cg-Tg(Thy1-COL25A1)861Yfu/J

Stock number: 012597
Research areas: Developmental Biology Research, Neurobiology Research

Description

Mice hemizygous for the Thy1-COL25A1 allele contain a human Collagen XXV alpha 1 (COL25A1) gene under the control of the mouse Thy1.2 promoter, leading to expression of human COL25A1 in the cortex and the hippocampus. These mice may be useful for studying the accumulation of protease-resistant plaques in the pathogenesis of Alzheimer's Disease.

Detailed description

Mice hemizygous for the Thy1-COL25A1 allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Collagen XXV alpha 1 (COL25A1), also known as collagen-like Alzheimer's amyloid plaque component precursor, is a type II transmembrane protein expressed in neurons that colocalizes with Amyloid β (Aβ) in senile plaques in the brains of Alzheimer's patients. In the Thy1-COL25A1 mouse, overexpression of human COL25A1 is regulated by a murine Thy1.2 promoter (Thy1), which leads to expression in the cortex and the hippocampus. This overexpression results in accumulation of Aβ and increased levels of p35/p25 and β-site APP-cleaving enzyme 1 (BACE1), which may induce synaptic dysfunction leading to the behavioral changes associated with Alzheimer's Disease. COL25A1 precursor is expressed in cell membranes of cortical neurons, in 2 month old mice. At 6 months, COL25A1 precursor was expressed in the cortex, CA1 pyramidal neurons, dentate gyrus (DG), granule neurons, and thalamic cells, while secreted forms of were detected in extracellular matrix (ECM) of cortex and DG and formed fibrillar ECM deposits. In 1-year-old mice, both forms of COL25A1 were detected in the entire brain. These mice may be useful for studying the accumulation of protease-resistant plaques in the pathogenesis of Alzheimer's Disease.

Development

The Thy1-COL25A1 transgene contains a human Collagen XXV alpha 1 (COL25A1) gene under the control of the mouse Thy1.2 promoter. The construct was microinjected into fertilized oocytes obtained from matings of (C57BL/6 x SJL)F1, and the donating investigator reported that offspring from founder line 861 were backcrossed to C57BL/6J (see SNP note below) for at least 14 generations to establish a colony. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Tg(Thy1-COL25A1)861Yfu
Name: transgene insertion 861, Ying-Hui Fu
MGI accession ID: MGI:4359741
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Thy1-COL25A1)861Yfu
Marker name: transgene insertion 861, Ying-Hui Fu
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: COL25A1,collagen type XXV alpha 1 chain,human
Molecular note: A human COL25A1 complementary cDNA (AF293340, nt507-2588 splice variant lacking nt952-969) was placed under the control of the Thy1 promoter. The protein product corresponds to AAK35008 without amino acids 141-146 in the COL1 domain. Two founders (861, and 797) showed abundant transgene expression.