B6.129X1(Cg)-Nectin1^tm1Ytk/J

Stock number: 008116
Research areas: Developmental Biology Research, Neurobiology Research, Sensorineural Research

Description

Mice that are homozygous for this targeted mutation exhibit microthalmia, abnormal eye morphology, reduced number of puncta adherentia junctions at the synapses between mossy fibers and CA3 pyramidal cell dendrites, and misprojection of mossy fibers. This mutant mouse strain may be useful in studies of eye development, mossy fiber trajectory in neurodevelopment and herpes simplex virus (HSV) infection.

Detailed description

Mice that are homozygous for the targeted mutation are viable, fertile, and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by Western blot analysis of brain extracts from homozygotes. The Donating Investigator reports that homozygous mice are smaller than wild-type littermates until they are six months of age. 30% of homozygotes are born with one or both eyes open. Homozygotes exhibit microthalmia, absent vitreous body, abnormal undulating retinal layers, deformed lenses with adhered ciliary epithelia and lack ciliary processes. At E16.5, the eyelids of homozygotes are not fused and the apex-apex junction of the pigmented and non-pigmented cell layers of the ciliary epithelia are separated. The number of puncta adherentia junctions at the synapses between mossy fibers and CA3 pyramidal cell dendrites is decreased. Mossy fiber projection through the hippocampus is abnormal. Homozygotes have abnormally long hippocampal infrapyramidal bundle, IPB. The Donating Investigator reports that they have experienced some difficulty obtaining homozygous females from matings of fully backcrossed (N10) mutant mice on the C57BL/6 background. This mutant mouse strain may be useful in studies of eye development, mossy fiber trajectory in neurodevelopment and herpes simplex virus (HSV) infection.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2, which encodes amino acids 26-143. The construct was electroporated into 129X1/SvJ derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The mice were crossed to DBA mice and were then backcrossed to C57BL/6 for 10 generations.

Allele

Symbol: Nectin1^tm1Ytk
Name: targeted mutation 1, Yoshimi Takai
MGI accession ID: MGI:3605480
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Nectin1
Marker name: nectin cell adhesion molecule 1
Chromosome: 9
Strain of origin: 129X1/SvJ
Molecular note: A construct was designed to replace sequence in exon 2 encoding amino acids 26-143 with a neomycin resistance gene. Absence of protein was confirmed by Western blot.