B6(C3)-Mybl1^repro9/JEbfJ

Stock number: 027889
Product name: repro9
Research areas: Reproductive Biology Research

Description

These mice carry an ENU-induced point mutation in the Mybl1 gene that results in homozygous male infertility due to meiotic arrest. MYBL1^repro9 protein is reduced but not absent in mutant testes.

Detailed description

Mybl1 (myeloblastosis oncogene-like 1; also called A-Myb) is a transcription factor that has been identified as a male-specific master regulator of several crucial meiotic processes.

These Mybl1^repro9 mice carry an ENU-generated point mutation (A213E) associated with homozygous male infertility. Testes exhibit a histopathological phenotype indistinguishable from that of Mybl1 knockout animals. Spermatocytes demonstrate subtle defects in autosome synapsis in pachynema, a high incidence of unsynapsed sex chromosomes, incomplete double-strand break repair on synapsed pachytene chromosomes, and a lack of crossing over. Homozygous females are fertile and viability is unaffected.

Homozygous Mybl1^repro9 mice do not exhibit the runting or abnormal breast development observed in homozygous knockout mice. This indicates that the mutation is a hypomorphic or separation-of-function allele that specifically impairs the spermatogenesis function of MYBL1. Western blot indicates that MYBL1^repro9 protein is reduced, but not absent in mutant testes.

Development

Male C57BL/6J (B6) mice were mutagenized with ethylnitrosourea (ENU) then bred to C3HeB/FeJ (C3H) females to create G₁ male founders at The Jackson Laboratory. These males were backcrossed to C3H females, and G₂ daughters were backcrossed to the G₁ male to yield G₃ offspring that were tested for infertility. Genome scans revealed a C to A transversion that results in a glutamic acid to alanine amino acid change at position 213 (A213E). This strain was backcrossed to C57BL/6J for 11 generations by the donating laboratory at Cornell University, then backcrossed for one generation to re-derive stock at The Jackson Laboratory.

Allele

Symbol: Mybl1^repro9
Name: reproductive mutant 9, JAX Reproductive Mutagenesis Program
MGI accession ID: MGI:3512907
Generation method: Chemically induced (ENU)
Marker symbol: Mybl1
Marker name: myeloblastosis oncogene-like 1
Chromosome: 1
Strain of origin: C57BL/6J
Molecular note: ENU mutagenesis induces a C to A transversion that results in the amino acid substitution of glutamic acid for alanine at position 213 (A213E).