STOCK Ash1l^{Gt(AL0395)Wtsi}/SacJ

Stock number: 028220
Product name: Ash1l^GT
Research areas: Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research

Description

This gene trap mutation of the Ash1l gene is a hypomorphic allele. These mice may be useful for studying the reproduction (fertility), and early embryonic growth and development.

Detailed description

The trithorax group transcription activator encoded by the ash1 (absent, small, or homeotic)-like (Drosophila), Ash1l, gene, functions as a histone methyltransferase that is important for the regulation of expression of Hox genes. These mice carry a hypomorphic β-geo gene trap allele of the Ash1l gene. Homozygotes have a partially penetrant perinatal lethal phenotype. Homozygous females are infertile because of decidualization and/or implantation failure, due to fewer endometrial uterine glands. Homozygous males exhibit reduced fertility due to structural abnormalities of the epididymis, resulting in a decrease in viable sperm exiting the vas deferens. Significantly reduced mRNA levels are detected by real-time quantitative RT-PCR of epididymides, ductus deferens and uterus tissue, and by in situ hybridization in the uterus. Immunohistochemical analysis of uterus tissue from 3 and 4 week old homozygous females and epididymis from homozygous males also shows diminished Ash1l gene product expression (protein). Homozygotes are smaller than wildtype littermates and are born with closed eyelids. Adult homozygotes lack meibomian glands in the eyelids, which are necessary for eye lubrication, resulting in chronic blepharitis. Abdominal fat is reduced and thoracic verterbral abnormalities (extra rib, abnormal rib attachment to sternum) are observed in mutants.

Development

A gene trap vector, pGT01xf, containing the β-geo reporter gene (β-galactosidase and neomycin resistance fusion gene) was inserted into intron 1 of the Ash1l gene. The construct was electroporated into 129P2/OlaHsd derived E14TG2a.4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J x (C57BL/6J x DBA/2J) F1 blastocysts. The resulting chimeric animals were tested for germline transmission. The strain was maintained on a C57BL/6J and DBA/2J background. 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: Ash1l^{Gt(AL0395)Wtsi}
Name: gene trap AL0395, Wellcome Trust Sanger Institute
MGI accession ID: MGI:3852878
Generation method: Gene trapped
Attributes: Hypomorph
Marker symbol: Ash1l
Marker name: ASH1 like histone lysine methyltransferase
Chromosome: 3
Strain of origin: 129P2/OlaHsd
Molecular note: A gene trap vector, pGT01xf, containing the beta-geo reporter gene (beta-galactosidase and neomycin resistance fusion gene) was inserted into intron 1 of the Ash1l gene. Immunohistochemical analysis of uterus tissue from 3 and 4 week old homozygous females and epididymis from homozygous males also shows diminished Ash1l protein.