B6.Cg-Snord116^tm1.1Uta/J

Stock number: 008149
Product name: 1-loxp (KO) , Snord116del
Research areas: Cell Biology Research, Developmental Biology Research, Internal/Organ Research, Metabolism Research, Neurobiology Research, Research Tools

Description

These Snord116del mice may be useful in studying growth and feeding regulation, mechanisms of obesity, and pathophysiology of Prader-Willi syndrome. Of note, mice harboring a loxP-flanked Snord116 cluster are also available (see Stock No. 008118).

Detailed description

Mice homozygous for this Snord116del (1-loxP or knockout) allele are viable and fertile. As the Snord116 gene cluster is imprinted and expressed only from the paternal allele, mice with paternal inheritance of the deletion lack expression of the targeted Snord116 small nucleolar RNAs (snoRNAs) gene cluster in brain tissues. Similarly, paternal transmission of the mutant allele is required to obtain the mutant phenotype in offspring. Affected heterozygotes (paternal deleted/maternal wildtype) recapitulate a subset of Prader-Willi syndrome (PWS) characteristics, including early-onset postnatal growth retardation, delayed sexual maturation, increased anxiety, motor learning deficit and hyperphagia (but not obesity). Other reported abnormalities include altered metabolic fuel usage, prolonged meal time, and increased levels of circulating ghrelin. These Snord116del mice may be useful in studying growth and feeding regulation, mechanisms of obesity, and pathophysiology of Prader-Willi syndrome.

Of note, mice harboring a loxP-flanked Snord116 cluster are also available (see Stock No. 008118).

Development

Two individual targeting vectors were used to place a loxP site (and an Frt1-flanked PGK-neo cassette) upstream, and a loxP site (and an Frt5-flanked puromycin resistance/TK cassette) downstream of the Snord116 cluster. The upstream targeting vector was transfected into C57BL/6-derived Bruce-4 embryonic stem (ES) cells, and correctly targeted ES cells were next transfected with the downstream targeting vector. Doubly targeted ES cells were then transiently transfected with a cre expressing plasmid. The resulting 1-loxP ES cells (with the Snord116 cluster deleted and a single loxP site remaining) were injected into recipient blastocysts. Chimeric males were bred to albino B6(Cg)-Tyr^c-2J/J (Stock No. 000058) females. The mutant 1-loxP mice were then bred to C57BL/6J inbred mice for 5 generations prior to arrival at The Jackson Laboratory.

Allele

Symbol: Snord116^tm1.1Uta
Name: targeted mutation 1.1, Uta Francke
MGI accession ID: MGI:3773673
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Snord116
Marker name: small nucleolar RNA, C/D box 116 cluster
Chromosome: 7
Strain of origin: B6.Cg-Thy1^a
Molecular note: Two individual targeting vectors were used to place a loxP site (and an Frt1-flanked PGK-neo cassette) upstream, and a loxP site (and an Frt5-flanked puromycin resistance/TK cassette) downstream of the Snord116 cluster. The upstream targeting vector was transfected into C57BL/6-derived Bruce-4 embryonic stem (ES) cells, and correctly targeted ES cells were next transfected with the downstream targeting vector. Doubly targeted ES cells were then transiently transfected with a cre expressing plasmid. The resulting 1-loxP ES cells (with the Snord116 cluster deleted and a single loxP site remaining) were injected into recipient blastocysts.