The targeted Esr1 gene encodes a ligand-activated transcription factor and nuclear estradiol hormone receptor. In the ERKO line (Stock #004744) multiple transcript variants may form due to alternative cryptic splicing of the endogenous mouse Esr1 gene. These mice carry an insertional disruption mutation of the Esr1 gene in which exon 2 has been deleted and a series of stop codons have been inserted. Two truncated mutant transcripts and a truncated protein (approximately 61kDa in size) having a deleted N-terminus are detected in uterine tissue from homozygous female mice by RT-PCR and Western blot analysis.
At birth, mice homozygous for the targeted allele are viable and normal in size and appearance. Female homozygous mice are infertile, exhibit cystic ovaries that lack corpora lutea and have hypoplastic uteri that are unresponsive to estrogen. Homozygous males are infertile, low normal testis weight as adults and diminished sperm count (10% of normal.
Homozygous females have more than 4-fold higher level of serum estradiol and elevated androgen levels compared to wildtype controls, indicative of estrogen insensitivity. There is approximately 3% of the Estradiol binding in uterine tissue from homozygotes compared to levels observed in wildtype controls; no estradiol binding is detected in other tissues (brain, kidney, and liver) from homozygotes. Female neuroendocrine estrogen negative feedback is disrupted with highly elevated LH, normal FSH levels but no prolactin.
Please note: Mice carrying this Esr1tm1Ksk allele (Stock No. 004744), express a low level of a truncated form of ERα, the result of alternate splicing of the transcript. In contrast, mice carrying the Esr1tm4.2Ksk allele (Stock No. 026176) have no tissue responses to estrogen and no estrogen receptor alpha activity.
