| First Author | Harris BS | Year | 2017 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:238326 |
| Mgi Id | MGI:5819057 | Citation | Harris BS, et al. (2017) The blunt face mutation of latent transforming growth factor beta binding protein 3. MGI Direct Data Submission |
| abstractText | The blunt face mutation, blfc, arose spontaneously at The Jackson Laboratory in the strain LT.MA-Glo1 H2/J. By two weeks of age homozygotes are smaller than their unaffected littermates, and the face appears shorter, with a blunted nose and wide-set eyes that can appear to protrude more than normal. Some mutants are scarcely half the normal size at two weeks of age, and some die before wean age. As they mature the body size remains only two-thirds to three-quarters normal size. Pathology revealed no abnormal lesions in five mice at 6 to 18 months of age except for one homozygote with mild temporomandibular joint degeneration. X-rays of one homozygote found no abnormalities in the long bones or spine, and the mineralization and growth plates appeared normal, but the orbits of the skull were round, not oblong, and the craniofacial deformity was evident. Eye examinations of one female homozygote at two months of age showed a corneal hole in the right eye and an iris coloboma in the left, with that cornea having an optic cup ring. Two male homozygotes at two months of age each had corneal holes. Eye examinations of two heterozygous females at two months of age were normal. This strain has smaller than normal litter size and reduced fertility: of 31 breeder pairs of homozygous females crossed to heterozygous males, twenty-two were non-productive; of eleven pairs of heterozygous intercrosses two were non-productive; of thirty-two pairs of heterozygous females crossed to homozygous males seventeen were non-productive; and one pair bred homozygote to homozygote was non-productive. In a mapping cross to A/J, all of nine homozygotes were concordant with rs3705162 at Chromosome 19 position 5,732,295 bp, and three of these eighteen meioses showed recombination with rs3662712 at Chromosome 19 position 16,687,131 bp (GRCm38.p3). Whole exome sequencing identified several variants in genes near this map position and further characterization confirmed that the blfc mutation is a G to T single base pair change in Chromosome 19 position 5,751,407 bp. This is predicted to cause an E660STOP nonsense mutation in exon 19 of latent transforming growth factor beta binding protein 3 (Ltbp3). |
