A Hydrocephalus Mutation with Rhinitis on Mouse Chromosome Eight

Authors:Louise Dionne, Michelle Curtain, Leah Rae Donahue

Source of Support: NIH-NEI grant EY015073 to Leah Rae Donahue

Mutation (allele) symbol: hyrh

Mutation (allele) name: hydrocephalus with rhinitis

Strain of origin: B10.RIII-H2rH2-T18b/(71NS)SnJ

Current strain name: B6.Cg-hyrh/J

Stock #: 006428 (view JAX® Mice Data Sheet for additional information including Price and Supply Information)

Phenotype categories: craniofacial

Abstract

A spontaneous, recessive hydrocephalus mutation with rhinitis has been identified and mapped to Chromosome 8.

Origin and Description

 

Mice carrying this new mutation were discovered in a colony of B10.RIII-H2r-T18 b/(71NS)SnJ (Stock# 00457) at the Jackson Laboratory. The mutation is now an incipient congenic on the C57BL/6J (Stock # 000664) since it has been crossed to this background five times. Homozygotes are recognized by smaller bodies and domed skulls and do not live beyond three weeks, as the hydrocephalic condition is unremitting and only worsens. The B6.Cg-hyrh/J colony is maintained by ovarian transplant surgery taking ovaries from an hyrh/hyrh female and transplanting them into a C3SnSmn.CB17-Prkdcscid/J (Stock # 001131) host female. The female hosts are either mated to a C57BL/6J wild-type male and +/hyrh offspring are subsequently mated to produce mutants, or the female hosts are mated to a +/hyrh from the colony.

 

Genetic Analysis

Hydrocephalus with rhinitis (hyrh) was determined to be recessive when female hyrh/hyrh ovaries were transplanted into a C3SnSmn.CB17-Prkdcscid/J female, this host female was then mated to a C57BL/6J male wild type and hyrh mutants were observed only in the F2 litters.

Using our standard mapping protocol the hyrh mutation maps to Chromosome 8 between markers D8Mit86 at 108.2Mb and D8Mit165 at 111.45 Mb. There were no recombinants at D8Mit151 at 109.9 Mb and D8MIT316 at 110.5 Mb. In this region at 109.6 Mb is the Hydin gene. Due to the chromosomal location and similarity of phenotypes between the Hydin  mutants and the hyrh phenotype, a complementation test was performed. +/Hydinhy3 mice were bred with +/hyrh mice and there were no affected mice from 114 born; therefore the two mutations are not allelic. 

Pathology

 

A pathological screen of 7 hyrh mutants was performed ranging from one to three weeks of age. Two mutants were assessed at one weak of age and each was found to have moderate rhinitis but a healthy thymus. However, two-week-old mutants had developed acute rhinitis and an atrophic thymus and two other mutants had hydrocephalus and severe acute rhinitis; age-matched controls had none of these conditions. One mutant at three weeks of age had severe hydrocephalus and rhinitis. Histological sections were prepared from a two week old mutant's middle ear to evaluate for otitis media and infections were not detected.

Discussion

 

Hydrocephalus with rhinitis (hyrh) mutants get rhinitis as early as one week after birth. Their health continues to decline as hydrocephalus develops and rhinitis worsens.

 

Acknowledgements

 

We wish to thank Ezra O'Connor for discovering the the mice carrying the new hyrh mutation; Coleen Kane for preparation of tissues for histological assessment; Rod Bronson, for pathological evaluation, Victoria DeMambro for mapping the mutation and Pat Ward-Bailey for web posting.