| Primary Identifier | MGI:1857299 | Allele Type | Spontaneous |
| Gene | Hprt1 | Transmission | Germline |
| Strain of Origin | 129P2/OlaHsd | Is Recombinase | false |
| Is Wild Type | false |
| description | HPRT- embryonic stem cells were obtained by selecting for spontaneous mutation by incubation in medium containing 6-thioguanine. HPRT- males have no overt phenotype of abnormal behavior (J:15483). The mutation is due to a large deletion in the Hprt gene. In situ hybridization studies showed HPRT mRNA in high levels in most neurons, but not in glial cells, in normal mice. No HPRT mRNA was detected in the brains of male mice carrying this deletion (J:2058). Mutant mice have no HPRT detectable by Western blot analysis and no detectable HPRT enzyme activity in brain homogenates. They appear to have normal brain purine content, but de novo purine synthesis is accelerated four- to fivefold (J:11842). The Hprtb-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt are activated during early embryonic development (J:2389). Either administration of amphetamine (J:1847) or inhibition of adenine phosphoribosyltransferase (APRT) activity (J:4123) stimulates locomotor and stereotypic behaviors in HPRT-deficient mice. However, the null mutant for both Hprt and Aprt does not show the characteristics of Lesch-Nyhan disease (J:35822). Cells from mice hemizygous or homozygous for this mutation are HPRT-deficient and resistant to the drug 6-thioguanine (6TG). |
| molecularNote | The allele contains a ~55 kb deletion spanning the promoter and first 2 exons. Subsequent direct sequence comparison with wild type DNA defined the exact breakpoints of the deletion, which lies 415 bp after the 3' end of exon 2, and determined the deletion size to be 36 kb (chrX:52,052,497-52,088,500 MM39). |
