NOD.Cg-Foxn1^em1Dvs/J

Stock number: 029390
Product name: NOD-nude , NOD-Foxn1^null
Research areas: Cancer Research, Cardiovascular Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools, Virology Research

Description

NOD-nude mice harbor a CRISPR-made Foxn1 knock-out allele (Foxn1^null) on the non-obese diabetic (NOD/ShiLtJ) genetic background. Foxn1-deficient mice are athymic (lack T cells and cell-mediated immunity) and immunodeficient, with functional-but-faulty hair growth follicles (hairless ["nude"] appearance).

Detailed description

NOD-nude (or NOD-Foxn1^null) mice are non-obese diabetic animals (NOD/ShiLtJ) with the Foxn1^em1Dvs knock-out allele (Foxn1^null). The Foxn1^null mutation has a 1 nucleotide deletion that causes a frame shift and premature truncation after an additional out-of-frame ~120 nucleotides - resulting in a 300 aa protein that is a functional knock-out.

These NOD-nude mice may be expected to combine the NOD phenotype (Stock No. 001976) with the Foxn1^nu spontaneous knock-out phenotype (Stock No. 000819). The expected phenotype of NOD-nude mice is described below.
Foxn1-deficient mice have no thymus (lack T cells and cell-mediated immunity) with functional-but-faulty hair growth follicles (hairless ["nude"] appearance). Foxn1-deficient females are poor mothers as they are unable to keep pups warm and have poor lactation. Whereas NOD mice heterozygous for Foxn1^null develop spontaneous autoimmune type 1 diabetes, NOD mice homozygous for Foxn1^null may be expected to attenuate or prevent diabetic phenotype.

Development

NOD-nude (or NOD-Foxn1^null) mice are non-obese diabetic animals (NOD/ShiLtJ) with the Foxn1^em1Dvs knock-out allele (Foxn1^null).

The Foxn1^em1Dvs knock-out allele (Foxn1^null) was created by the Type 1 Diabetes Repository (Dr. David V. Serreze) at The Jackson Laboratory using CRISPR/Cas9 genome engineering in NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/J mouse zygotes (NSG ; Stock No. 005557). The forkhead box N1 locus (Foxn1) on chromosome 11 was targeted with a specific single guide RNA (sgRNA) to create a 1 nucleotide deletion (GGCcAACGCCG to GGC-AACGCCG) in exon 5 (encodes the N-terminal portion of the DNA binding domain). This 1 nucleotide deletion causes a frame shift and premature truncation after an additional out-of-frame ~120 nucleotides - resulting in a 300 aa protein. The founders were bred to NSG mice, and the offspring were bred together to produce the NSG-Foxn1^null colony (NSG-nude ; Stock No. 026263). Some NSG-nude animals were bred to NOD/ShiLtJ inbred mice (Stock No. 001976) to remove the Prkdc^scid and Il2rg^tm1Wjl mutations. The resulting NOD/ShiLtJ-congenic Foxn1^null animals (NOD-nude) are Stock No. 029390.

Allele

Symbol: Foxn1^em1Dvs
Name: endonuclease-mediated mutation 1, David V Serreze
MGI accession ID: MGI:5882743
Generation method: Endonuclease-mediated
Attributes: Null/Knockout
Marker symbol: Foxn1
Marker name: forkhead box N1
Chromosome: 11
Strain of origin: NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ
Molecular note: CRISPR/cas9 endonuclease mediated genome editing is used to introduce a 1 nucleotide deletion (GGCcAACGCCG to GGC-AACGCCG) in exon 5 (encodes the N-terminal portion of the DNA binding domain). This 1 nucleotide deletion causes a frame shift and premature truncation after an additional out-of-frame ~120 nucleotides - resulting in a 300 aa protein.