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 language | English (US) |
|---|---|
| Pages (from-to) | 555-559 |
| Number of pages | 5 |
| Journal | Mammalian Genome |
| Volume | 4 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 1993 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - The little (lit) mutation cosegregates with the growth hormone releasing factor receptor on mouse Chromosome 6
AU - Chua, Jr., Streamson C.
AU - Hennessey, Karen
AU - Zeitler, Phillip
AU - Leibel, Rudolph L.
PY - 1993/10
Y1 - 1993/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0027762328&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027762328&partnerID=8YFLogxK
U2 - 10.1007/BF00361384
DO - 10.1007/BF00361384
M3 - Article
C2 - 8268652
AN - SCOPUS:0027762328
VL - 4
SP - 555
EP - 559
JO - Mammalian Genome
JF - Mammalian Genome
SN - 0938-8990
IS - 10
ER -