This knock-out allele of Ahi1 (Abelson helper integration site 1) is a deletion of exons 3-6, resulting in mice with a high homozygous postnatal lethality on the FVB/N background. Surviving knock-out mice are infertile, small and exhibit deficits in motor function. These mice may be useful for studying Joubert Syndrome, ciliogenesis and muscle development.
Russ Ferland, Albany Medical College
The Ahi1 (Abelson helper integration site 1) gene encodes a cytoplasmic multidomain protein involved in ciliogenesis and the development of photoreceptor outer segments. AHI1 is expressed in the hindbrain, midbrain and ventral forebrain. Mutations in Ahi1 are associated with the Joubert Syndrome, a neurodevelopment disorder, characterized by retinal dystrophy and defects in hindbrain development, as well as include deficits in motor and muscle function. Ahi1 knock-out (KO) mice contain a lacZ/neomycin cassette designed to replace exons 3-6. The donating investigator reports that the lacZ expression can not be detected. Mice that are heterozygous for the targeted mutation are viable and fertile. On the C57BL/6 background, Ahi2-/- mice die at birth. On the FVB/NJ background, 40% of homozygous pups die by postnatal day 2, of the survivors 70% die prior to postnatal day 10; survivors live to adulthood but are infertile and smaller in size than littermates. In addition, homozygous KO mice on the FVB/NJ background develop delayed reflex righting (neonate), reduced grip strength, reduced spontaneous locomotor activity, reduced muscle mass, myonuclear domain and muscle fiber cross-sectional area, but do not exhibit any gross malformations of the cerebellum. These mice may be useful for studying Joubert Syndrome, ciliogenesis and muscle development.
The Ahi1tm1Rujf allele is also distributed on the BALB/cJ genetic background (See MMRRC Stock No. 065561)
A targeting vector containing a lacZ/neomycin resistance cassette was used to disrupt exons 3-6. The construct was electroporated into B6.Cg-Thy1a derived Bruce4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J females, offspring were backcrossed to FVB/NJ for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.
|Allele Name||targeted mutation 1, Russell J Ferland|
|Allele Type||Targeted (Reporter, Null/Knockout)|
|Allele Synonym(s)||Ahi1tm1Rujf; targeted mutation 1, Russell J Ferland|
|Gene Symbol and Name||Ahi1, Abelson helper integration site 1|
|Gene Synonym(s)||AHI-1; dJ71N10.1; Jouberin; D10Bwg0629e; D10Bwg0629e; DNA segment, Chr 10, Brigham & Women's Genetics 0629 expressed; ORF1; JBTS3; 1700015F03Rik; RIKEN cDNA 1700015F03 gene; Ahi-1; 1700015F03Rik; Ahi-1|
|Strain of Origin||B6.Cg-Thy1a|
|Molecular Note||Exons 3 through 6 were replaced with a lacZ/neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts.|
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or FVB/NJ inbred mice. Mice homozygous for the mutation are infertile.
When using the Ahi1- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #65562 in your Materials and Methods section.
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