B6.129-Abca2^tm1Kdt/J

Stock number: 012465
Research areas: Neurobiology Research

Description

This Abca2 knockout strain may be useful in studies of myelin sheath development, oligodendrocyte differentiation, tremor without ataxia, and hyperactivity.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Although homozygotes are viable and fertile, few pups born to homozygous females survive. The Donating Investigator maintains the C57BL/6 congenic strain using heterozygous crosses. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of cerebrum, cerebellum, spinal cord, heart, lung, kidney, liver, spleen, thymus, uterus, prostate, and ovary. Homozygotes exhibit a quivering or shaking phenotype and are more easily startled by sound, hence the "skittish" nickname designation. The tremor is without ataxia. Homozygotes exhibit hyperactivity. Although growth rate and food consumption are similar to wildtype controls, homozygotes have a reduced body weight. The observed hyperactivity and reduced body weight is more significant in female homozygotes. Ultrastructural analysis of myelin sheath in cerebrum and spinal cord reveals increased myelin sheath thickness in the spinal cord and defective myelin compaction (membrane periodicity) in both spinal cord and cerebrum. An increased number of mitochondria is observed by ultrastructural analysis of sciatic nerve.

When crossed with TRAMP transgenic mice (Stock No. 003135) the double mutant mice, 20-25 weeks in age, exhibit no detectable metastases, while 38% of wild-type littermates carrying the TRAMP transgene alone developed metastases in the lung and/or lymph nodes.

Development

A targeting vector containing a Neo selection cassette was used to disrupt exons 23 through 30, which encodes the first nucleotide-binding domain of the transporter. The construct was electroporated into 129/Sv derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The mice were backcrossed to C57BL/6J for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Abca2^tm1Kdt
Name: targeted mutation 1, Kenneth D Tew
MGI accession ID: MGI:3697467
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Abca2
Marker name: ATP-binding cassette, sub-family A (ABC1), member 2
Chromosome: 2
Strain of origin: 129/Sv
Molecular note: Exons 23-30 were replaced with a neomycin resistance cassette. This sequence encoded the first nucleotide binding domain.