B6.129-Gfi1^{tm3(Gfib1)Tmo}/J

Stock number: 016163
Product name: Gfi1:Gfi1b knock-in
Research areas: Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools, Sensorineural Research

Description

Gfi1:Gfi1b knock-in mice express mouse Gfi1b (growth factor independent 1B) from the endogenous Gfi1 (growth factor independent 1) locus and may be useful in studies of deafness, hematopoiesis, and lymphopoiesis.

Detailed description

These mutant mice express mouse Gfi1b (growth factor independent 1B) from the endogenous Gfi1 locus. Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. Higher expression levels of Gfi1b transcript is detected in inner ears as measured by RT-PCR analysis. The Gfi1b knock-in did not completely rescue the Gfi1 knock out phenotype (see STOCK No. 016161). Homozygotes have slightly fewer granulocytes in bone marrow, a small accumulation in bone marrow of immature myeloid cells and monocytes, and fewer mature circulating granulocytes when compared to wildtype controls. At 3 to 3.5 months in age, homozygotes are deaf, do not display a Preyer reflex, abnormal auditory brainstem response (over 100 dB at 8 kHz and over 90 dB at 16 and 32 kHz), and exhibit head bobbing and abnormal reaching response. In neonatal mutants, the cochlear inner hair cells are morphologically immature and the outer hair cells are smaller in size and disorganized with progressive degeneration. The cochlear phenotype is less severe in these mice when compared to the knock-out mice. During backcrossing, the Y chromosome may not have been fixed to the C57BL/6 genetic background.

Development

A targeting vector containing a loxP-flanked NEO selection cassette and Gfi1b (growth factor independent 1B) cDNA was used to disrupt exons 2 through 5, the entire coding region. The Gfi1b cDNA was inserted immediately downstream of the Gfi1 translation initiation codon. Correctly targeted ES cells were injected into recipient blastocysts. Heterozygote mice were crossed to CMV-cre transgenic mice (on the C57BL/6 background) to remove the floxed NEO selection cassette. The mice were then backcrossed to C57BL/6 for 14 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: Gfi1^{tm3(Gfib1)Tmo}
Name: targeted mutation 3, Tarik Moroy
MGI accession ID: MGI:3695403
Generation method: Targeted
Marker symbol: Gfi1
Marker name: growth factor independent 1 transcription repressor
Chromosome: 5
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: Gfi1b,growth factor independent 1B,mouse, laboratory
Molecular note: The coding region was replaced with growth factor independent 1B cDNA.