In 2014, CHDI Foundation colony Stock No. 370476 [CHDI-81003003] heterozygous animals with ~190 CAG repeat length were sent to The Jackson Laboratory Repository, from which B6J.zQ175 KI heterozygotes are available as 027410.
Marie-Francoise Chesselet, University of California, Los Angeles
Dr. David Howland, CHDI Foundation
Daniela Brunner, PsychoGenics Inc.
The zQ175 knock-in (zQ175 KI) allele was derived from a spontaneous expansion of the CAG copy number in CAG140 knock-in (CAG 140 KI) mice as described below. The zQ175 knock-in (zQ175 KI) mouse was generated by Drs. Scott Zeitlin (University of Virginia) and Marie-Francoise Chesselet (University of California, Los Angeles) and colleagues.
A fragment extending from 18 bp upstream of huntingtin (Htt; HD or Hdh) exon 1 to 100 bp into intron 1 was replaced with human HTT sequence containing 140 repeats of a pure CAG tract [(CAG)nCAACAG, encoding polyglutamine]. A floxed neo cassette was retained 1.3 kbp upstream of exon 1. The targeting vector was microinjected into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived W9.5/W95 embryonic stem (ES) cells. While backcrossing onto C57BL/6J at PsychoGenics, germline expansions of the CAG tract led to the identification of a mouse with 175 CAG repeats. This mouse was selectively bred to create a new subline, named zQ175 (with the letter z used to identify that the line was derived from a line created by Scott Zeitlin). Subsequently, the CAG repeat number in zQ175 expanded further, and a line was selectively stabilized with ~190 CAG repeats. This line is identical in construct to CAG 140 KI mice except for CAG tract size. The zQ175 KI mice have been backcrossed with C57BL/6J inbred mice (Stock No. 000664) five or more generations to create the C57BL/6J-congenic colony (B6J.zQ175 KI). In 2014, heterozygous animals with ~190 CAG repeat length were sent from the CHDI Foundation colonies to The Jackson Laboratory Repository. zQ175 KI heterozygotes are available as Stock No. 370476 [CHDI-81003003].
|Allele Name||targeted mutation 1, Marie-Francoise Chesselet|
|Allele Type||Targeted (Humanized sequence)|
|Allele Synonym(s)||140-CAG KI; CAG140; CAG140 KI; HdhQ140; Q140; Q175 KI; zQ175|
|Gene Symbol and Name||Htt, huntingtin|
|Strain of Origin||129S1/Sv-Oca2+ Tyr+ Kitl+|
|Molecular Note||A fragment extending from 18 bp upstream of the polyglutamine stretch in exon 1 to 100 bp into intron 1 was replaced with human HD sequence containing 140 CAG repeats. A floxed neo cassette was retained 1.3 kb upstream of exon 1. Western blot analysis of homozygous mutant cerebellum and forebrain tissues identified protein corresponding with the mouse/human hybrid protein. Similar levels of mutant and endogenous protein were observed. The repeat number is not stable and may expand or contract.|
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