The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse Chromosome 6

Streamson C. Chua, Jr., Karen Hennessey, Phillip Zeitler, Rudolph L. Leibel

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The little (lit) autosomal recessive mutation in the mouse causes dwarfism due to isolated growth hormone deficiency. The in vitro physiology of pituitary growth hormone release in lit/lit animals suggests that an abnormality in the growth hormone releasing factor (GRF) receptor (Ghrfr) is a very likely candidate for the lit mutation. We mapped Ghrfr to the region around lit on Chromosome (Chr) 6 in 100 chromosomes of an FVB x Czech II interspecific backcross. Molecular markers were Neuropeptide Y (Npy), homeobox (Hoxa2), immunoglobulin kappa chain (Igk), wingless-related MMTV integration site (Wnt-2), cystic fibrosis (Cftr), carboxypeptidase A (Cpa), and Ghrfr. Map order and distances were as follows: Cen-//-Wnt-2-(0 cM)-Cftr-(6.0 cM)-Cpa-(8.0 cM)-Npy-(1.0 cM)-Hoxa2-(3.0 cM)-Ghrfr-(2.0 cM)-Igk. We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2 chromosomes of offspring of a B6CZ lit/ + x B6FVB lit/ + intercross and 18 chromosomes of offspring of a B6FVB lit/ + intercross. Map order and distances were as follows: Hoxa2-(2.1 cM)-lit/Ghrfr-(3.7 cM)-Igk. No recombinations between lit and Ghrfr were detected. Thus, Ghrfr maps to mouse Chr 6 and may be allelic with lit. Amplification of a short segment at the 3′ end of the Ghrfr mRNA by reverse transcription coupled to the polymerase chain reaction showed a greatly diminished level of GRF receptor mRNA in the pituitaries of lit/lit mice as compared with lit/ + controls. Low level of message could reflect a primary molecular defect or be due to secondary hypoplasia of somatotropes. These genetic and molecular data suggest that the Ghrfr gene is mutated in the lit mouse.

Original languageEnglish (US)
Pages (from-to)555-559
Number of pages5
JournalMammalian Genome
Volume4
Issue number10
DOIs
StatePublished - Oct 1993
Externally publishedYes

Fingerprint

Immunoglobulin kappa-Chains
Growth Hormone-Releasing Hormone
Chromosomes, Human, Pair 6
Carboxypeptidases A
Mutation
Neuropeptide Y
Chromosomes
Pituitary Dwarfism
Chromosomes, Human, Pair 18
Dwarfism
Messenger RNA
Homeobox Genes
Cystic Fibrosis
Genetic Recombination
Growth Hormone
Reverse Transcription
Molecular Biology
Phenotype
Polymerase Chain Reaction
Genes

ASJC Scopus subject areas

  • Genetics

Cite this

The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse Chromosome 6. / Chua, Jr., Streamson C.; Hennessey, Karen; Zeitler, Phillip; Leibel, Rudolph L.

In: Mammalian Genome, Vol. 4, No. 10, 10.1993, p. 555-559.

Research output: Contribution to journalArticle

Chua, Jr., Streamson C. ; Hennessey, Karen ; Zeitler, Phillip ; Leibel, Rudolph L. / The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse Chromosome 6. In: Mammalian Genome. 1993 ; Vol. 4, No. 10. pp. 555-559.
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abstract = "The little (lit) autosomal recessive mutation in the mouse causes dwarfism due to isolated growth hormone deficiency. The in vitro physiology of pituitary growth hormone release in lit/lit animals suggests that an abnormality in the growth hormone releasing factor (GRF) receptor (Ghrfr) is a very likely candidate for the lit mutation. We mapped Ghrfr to the region around lit on Chromosome (Chr) 6 in 100 chromosomes of an FVB x Czech II interspecific backcross. Molecular markers were Neuropeptide Y (Npy), homeobox (Hoxa2), immunoglobulin kappa chain (Igk), wingless-related MMTV integration site (Wnt-2), cystic fibrosis (Cftr), carboxypeptidase A (Cpa), and Ghrfr. Map order and distances were as follows: Cen-//-Wnt-2-(0 cM)-Cftr-(6.0 cM)-Cpa-(8.0 cM)-Npy-(1.0 cM)-Hoxa2-(3.0 cM)-Ghrfr-(2.0 cM)-Igk. We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2 chromosomes of offspring of a B6CZ lit/ + x B6FVB lit/ + intercross and 18 chromosomes of offspring of a B6FVB lit/ + intercross. Map order and distances were as follows: Hoxa2-(2.1 cM)-lit/Ghrfr-(3.7 cM)-Igk. No recombinations between lit and Ghrfr were detected. Thus, Ghrfr maps to mouse Chr 6 and may be allelic with lit. Amplification of a short segment at the 3′ end of the Ghrfr mRNA by reverse transcription coupled to the polymerase chain reaction showed a greatly diminished level of GRF receptor mRNA in the pituitaries of lit/lit mice as compared with lit/ + controls. Low level of message could reflect a primary molecular defect or be due to secondary hypoplasia of somatotropes. These genetic and molecular data suggest that the Ghrfr gene is mutated in the lit mouse.",
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