These PWS-ICdel mutant mice have a targeted mutation of small nuclear ribonucleoprotein N gene (Snrpn) locus, and exhibit postnatal lethality and failure to thrive when the PWS-ICdel mutation is paternally inherited. These PWS-ICdel mutant mice may be useful in studying the Prader Willi syndrome imprinting center.
James Resnick, University of Florida
When females heterozygous for the PWS-ICdel mutation are bred with wildtype males, the resulting offspring are viable and fertile as adults. In contrast, paternal transmission of the PWS-ICdel mutation results in neonatal lethality between 1-7 days of age (failure to thrive) due to imprinting defects. Most of these pups will die within 48 hours, however, a few live to 7 days. Pups are underweight, unable to support themselves, dehydrated and weak. Although capable of nursing, little milk is observed in their stomachs and they develop low blood glucose levels. Of note, removing all but one wildtype littermate improves mutant mouse survivability. In addition, mutant mouse viability may be greatly improved by outcrossing to FVB/NJ females. These PWS-ICdel mutant mice may be useful in studying the Prader Willi syndrome imprinting center.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 35 kB of genomic DNA replacing 16 kB of upstream sequence including the putative imprinting center (IC) and exons 1 through 6. The construct was electroporated into 129-derived J4(XO) embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The donating investigator reports that this strain is derived from neomycin resistant isolate 328. Initially, chimeric males were crossed to C57BL/6J females, however paternal transmission of the allele results in perinatal lethality. The donating investigator maintained these PWS-ICdel mutant mice by breeding heterozygous females to C57BL/6J males for at least 19 generations prior to sending to The Jackson Laboratory Repository. Upon arrival, females heterozygous for the PWS-ICdel mutation were bred with C57BL/6J inbred males (Stock No. 000664) to establish the colony.
|Allele Name||targeted mutation 2, Camilynn I Brannan|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||IC deletion; PWS-IC deletion; PWS-ICdel35kb; PWS-ICdel; deltaPWS-IC|
|Gene Symbol and Name||Snrpn, small nuclear ribonucleoprotein N|
|Gene Synonym(s)||2410045I01Rik; 2410045I01Rik; FE 294; FE 294 psi; FE294; FE294 psi; HCERN3; MGC:18604; MGC:30325; PWCR; Peg4; Pwcr1; RIKEN cDNA 2410045I01 gene; RT-LI; SM-D; SMN; SNRNP-N; SNURF-SNRPN; sm-N|
|Strain of Origin||129S/Sv|
|Mutations Made By|| |
Dr. Camilynn Brannan, Univ of Florida College of Medicine
Paternal transmission of the PWS-ICdel mutation results in neonatal lethality between 1-7 days of age due to imprinting defects.
For routine colony maintenance at The Jackson Laboratory Repository, heterozygous females are bred with wildtype males from the colony (or C57BL/6J inbred males); this results in offspring that are viable and fertile as adults.
If researchers want to generate PWS-ICdel offspring with the neonatal lethality phenotype, wildtype females from the colony (or C57BL/6J inbred females) may be bred with heterozygous males; this results in paternal transmission of the PWS-ICdel mutation. Of note, removing all but one wildtype littermate improves mutant mouse survivability. In addition, mutant mouse viability may be greatly improved by outcrossing to FVB/NJ females.
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