C57BL/6-Ddhd1^{Tg(ATXN2*Q22)2Past}/J

Stock number: 041859
Product name: ATXN2^Q22
Strain synonyms: B6J.B6-Ddhd1^{Tg(ATXN2*Q22)2Past}/J
Research areas: Cell Biology Research, Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

ATXN2^Q22 mice harbor a human ATXN2 transgene, containing 22 polyQ repeats, which is the most common polyQ repeat length in healthy individuals. These mice may be useful as a control to the mutant ATXN2^Q33 mouse line (Stock No. 041860) when studying amyotrophic lateral sclerosis (ALS) pathologies and respective therapeutics.

Detailed description

Ataxin 2 (coded by ATXN2) is an RNA-binding protein necessary for proper RNA processing, protein translation, and cell metabolism. ATXN2 harbors a trinucleotide CAG repeat sequence that results in the coded protein containing a polyglutamine (polyQ) tract. Healthy individuals typically express ~22 polyQ repeats; however, mutations in this gene may lead to expansions of the polyQ tract length, which have been associated with multiple neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Spinocerebellar Ataxia Type 2 (SCA2), and Parkinsonism. These ATXN2^Q22 transgenic mice express the entire human ATXN2 gene, containing ~22 polyQ repeats (ATXN2Q22; (CAG)13-CAA-(CAG)8).

Hemizygous ATXN2^Q22 mice are viable and fertile with no overt phenotype. The donating laboratory has not attempted to generate homozygous mice. Six copies of the ATXN2^Q22 transgene were confirmed to have integrated into an intronic region between exons 2 and 3 of the DDHD domain containing 1 (Ddhd1) gene. No changes in endogenous Ddhd1 expression were observed in the ATXN2^Q22 mice. These mice may be useful as a control to the mutant ATXN2^Q33 mouse line (Stock No. 041860) when studying ALS pathologies and respective therapeutics.

Development

A bacterial artificial chromosome (BAC) clone RP11-798L15, containing the 147kb human ataxin 2 (ATXN2) gene, as well as 25kb of the 5' and 4kb of the 3' flanking sequence. The BAC construct was created using a two-step BAC modification with PLD53.SC-AB vector and was further modified to harbor 22 polyglutamine repeats on the N-terminus (ATXN2Q22; (CAG)13-CAA-(CAG)8); this is the most common polyQ repeat in healthy individuals. The purified BAC was microinjected into fertilized C57BL/6 oocytes, and ATXN2^Q22 mice from founder line 2 were backcrossed to C57BL/6J mice for at least 6 generations by the donating laboratory. To establish a live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes.

Of note, the donating laboratory confirmed that 6 copies of the transgene have integrated into an intronic region between exons 2 and 3 of the DDHD domain containing 1 (Ddhd1) gene on chromosome 14.

Allele

Symbol: Ddhd1^{Tg(ATXN2*Q22)2Past}
Name: transgene insertion 2, Jeroen Pasterkamp
MGI accession ID: MGI:8386602
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Ddhd1
Marker name: DDHD domain containing 1
Marker synonyms: 4921528E07Rik; 9630061G18Rik; iPLA1alpha; iPLA1I; mKIAA1705; PAPLA1; PA-PLA1; SPG28
Chromosome: 14
Strain of origin: C57BL/6
Molecular note: A bacterial artificial chromosome (BAC) clone RP11-798L15, containing the 147kb human ataxin 2 (ATXN2) gene, as well as 25kb of the 5' and 4kb of the 3' flanking sequence, was created using a two-step BAC modification with PLD53.SC-AB vector and was further modified to harbor 22 polyglutamine repeats on the N-terminus (ATXN2Q22; (CAG)13-CAA-(CAG)8); this is the most common polyQ repeat in healthy individuals. The founder line 2 was characterized to have 6 copies of the transgene integrated into an intronic region between exons 2 and 3 of the DDHD domain containing 1 (Ddhd1) gene.