Removal of this mouse colony is imminent. If live mice are needed for your studies, it is advised that they be ordered immediately. After removal, the mice will be available from a cryorecovery.
PiZ mice express mutant human SERPINA1 (also known as AAT or α1-antitrypsin), which carries a glutamic acid to lysine substitution at residue 342 (E342K). PiZ mice accumulate α1-antitrypsin in hepatocytes and develop liver damage.
Christian Mueller, University of Massachusetts
SERPINA1 (serine (or cysteine) peptidase inhibitor, clade A, member 1 cluster, also known as AAT or α1-antitrypsin) is an abundant serine protease inhibitor expressed primarily in the liver. There are at least 30 variants of AAT found in humans, the most common being the PiM allele. Homozygosity for the PiZ allele, which differs from PiM by the amino acid substitution E342K (glutamic acid to lysine at residue 342), is associated with pulmonary emphysema, neonatal cholestasis, cirrhosis and hepatoma.
PiZ transgenic mice express the human AAT variant, PiZ, in both the liver and kidneys. Transgenic mice accumulate human α1-antitrypsin as cytoplasmic globular inclusions within the rough endoplasmic reticulum of hepatocytes. Homozygotes develop liver necrosis and inflammation with minimal fibrosis by 4 months of age. The concentration of circulating human AAT in heterozygous PiZ mice is comparable to the levels in PiZ/Z patients. This strain may be useful for studying liver disease.
Transgenic Tg(SERPINA1*E342K)#Slcw mice on a C57BL/6J background were obtained by Dr. Christian Mueller (University of Massachusetts).
The transgenic construct contains the entire mutant human SERPINA1 (serine (or cysteine) peptidase inhibitor, clade A, member 1 cluster) gene under its endogenous promoter plus 2 kB of the 5' and 3' flanking genomic DNA sequences. Mutant SERPINA1 contains the PiZ variant in which glutamic acid is replaced by lysine at residue 342 (CAG to AAG, E342K). The linearized construct was microinjected into fertilized (ICR x C57BL/6)F1 oocytes. Founder Z11.03 carrying 16 copies of the transgene was backcrossed to C57BL/6 for at least 5 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.
|Allele Name||transgene insertion Z11.03, Savio L C Woo|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Gene Symbol and Name||Tg(SERPINA1*E342K)Z11.03Slcw, transgene insertion Z11.03, Savio L C Woo|
|Site of Expression||expressed primarily in the liver|
|Strain of Origin||(ICR x C57BL/6)F1|
|General Note||The version of this allele that contains an unspecified founder number, Tg(SERPINA1*E342K)#Slcw, has been analyzed.|
|Molecular Note||The transgenic construct contains the entire mutant human SERPINA1 (serine (or cysteine) peptidase inhibitor, clade A, member 1 cluster) gene under its endogenous promoter plus 2 kB of the 5' and 3' flanking genomic DNA sequences. Mutant SERPINA1 contains the PiZ variant in which glutamic acid is replaced by lysine at residue 342 (CAG to AAG, E342K). Founder Z11.03 carrying 16 copies of the transgene.|
When maintaining a live colony, these mice can be bred by hemizygote or homozygote sibling matings. Please note: homozygotes develop liver necrosis by 4 months of age.
When using the PiZ mouse strain in a publication, please cite the originating article(s) and include JAX stock #035411 in your Materials and Methods section.